{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:30:23Z","timestamp":1792099823958,"version":"4.4.0"},"reference-count":133,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,3,25]],"date-time":"2016-03-25T00:00:00Z","timestamp":1458864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002790","name":"Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2015-05055"],"award-info":[{"award-number":["2015-05055"]}],"id":[{"id":"10.13039\/501100002790","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>A critical position in the developmental hierarchy is occupied by the Hox genes, which encode transcription factors. Hox genes are crucial in specifying regional identity along the embryonic axes and in regulating morphogenesis. In mouse, targeted mutations of Hox genes cause skeletal transformations and organ defects that can impair viability. Here, we present the current knowledge about the Hoxa5 gene, a paradigm for the function and the regulation of Hox genes. The phenotypic survey of Hoxa5\u2212\/\u2212 mice has unveiled its critical role in the regional specification of the skeleton and in organogenesis. Most Hoxa5\u2212\/\u2212 mice die at birth from respiratory distress due to tracheal and lung dysmorphogenesis and impaired diaphragm innervation. The severity of the phenotype establishes that Hoxa5 plays a predominant role in lung organogenesis versus other Hox genes. Hoxa5 also governs digestive tract morphogenesis, thyroid and mammary glands development, and ovary homeostasis. Deregulated Hoxa5 expression is reported in cancers, indicating Hoxa5 involvement in tumor predisposition and progression. The dynamic Hoxa5 expression profile is under the transcriptional control of multiple cis-acting sequences and trans-acting regulators. It is also modulated by epigenetic mechanisms, implicating chromatin modifications and microRNAs. Finally, lncRNAs originating from alternative splicing and distal promoters encompass the Hoxa5 locus.<\/jats:p>","DOI":"10.3390\/jdb4020013","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T16:00:28Z","timestamp":1459267228000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Hoxa5: A Key Player in Development and Disease"],"prefix":"10.3390","volume":"4","author":[{"given":"Lucie","family":"Jeannotte","sequence":"first","affiliation":[{"name":"Centre de recherche sur le cancer de l\u2032Universit\u00e9 Laval; CRCHU de Qu\u00e9bec, L\u2032H\u00f4tel-Dieu de Qu\u00e9bec, QC G1R 3S3, Canada"},{"name":"Department of Molecular Biology, Medical Biochemistry and Pathology, Universit\u00e9 Laval, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gotti","sequence":"additional","affiliation":[{"name":"Centre de recherche sur le cancer de l\u2032Universit\u00e9 Laval; CRCHU de Qu\u00e9bec, L\u2032H\u00f4tel-Dieu de Qu\u00e9bec, QC G1R 3S3, Canada"},{"name":"Department of Molecular Biology, Medical Biochemistry and Pathology, Universit\u00e9 Laval, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Landry-Truchon","sequence":"additional","affiliation":[{"name":"Centre de recherche sur le cancer de l\u2032Universit\u00e9 Laval; CRCHU de Qu\u00e9bec, L\u2032H\u00f4tel-Dieu de Qu\u00e9bec, QC G1R 3S3, Canada"},{"name":"Department of Molecular Biology, Medical Biochemistry and Pathology, Universit\u00e9 Laval, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1242\/dev.101.1.1","article-title":"The molecular basis for metameric pattern in the Drosophila embryo","volume":"101","author":"Akam","year":"1987","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/276565a0","article-title":"A gene complex controlling segmentation in Drosophila","volume":"276","author":"Lewis","year":"1978","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0092-8674(94)90290-9","article-title":"Hox genes in vertebrate development","volume":"78","author":"Krumlauf","year":"1994","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1242\/dev.001065","article-title":"The rise and fall of Hox gene clusters","volume":"134","author":"Duboule","year":"2007","journal-title":"Development"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tschopp, P., Tarchini, B., Spitz, F., Zakany, J., and Duboule, D. (2009). Uncoupling time and space in the collinear regulation of Hox genes. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000398"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ydbio.2010.04.024","article-title":"Hox genes and regional patterning of the vertebrate body plan","volume":"344","author":"Mallo","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/35001077","article-title":"Maintenance of functional equivalence during paralogous Hox gene evolution","volume":"403","author":"Greer","year":"2000","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.devcel.2006.06.016","article-title":"Reversal of Hox1 gene subfunctionalization in the mouse","volume":"11","author":"Tvrdik","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0070-2153(09)88003-4","article-title":"Hox specificity: Unique roles for cofactors and collaborators","volume":"88","author":"Mann","year":"2009","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1242\/dev.109785","article-title":"Cellular and molecular insights into Hox protein action","volume":"142","author":"Rezsohazy","year":"2015","journal-title":"Development"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nrg1726","article-title":"Modulating Hox gene functions during animal body patterning","volume":"6","author":"Pearson","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2013.10.012","article-title":"Human HOX gene disorders","volume":"111","author":"Quinonez","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00109-014-1181-y","article-title":"HOX genes and their role in the development of human cancers","volume":"92","author":"Bhatlekar","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1101\/gad.1.5.482","article-title":"Expression of a homeo domain protein in noncontact-inhibited cultured cells and postmitotic neurons","volume":"1","author":"Odenwald","year":"1987","journal-title":"Genes Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1101\/gad.7.11.2085","article-title":"Specification of axial identity in the mouse: Role of the Hoxa-5 (Hox1. 3) gene","volume":"7","author":"Jeannotte","year":"1993","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/(SICI)1097-0177(199805)212:1<141::AID-AJA13>3.0.CO;2-A","article-title":"Transcriptional interferences at the Hoxa4\/Hoxa5 locus: Importance of correct Hoxa5 expression for the proper specification of the axial skeleton","volume":"212","author":"Aubin","year":"1998","journal-title":"Dev. Dyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12644","DOI":"10.1073\/pnas.91.26.12644","article-title":"Homeotic transformation of cervical vertebrae in Hoxa-4 mutant mice","volume":"91","author":"Horan","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0925-4773(94)90073-6","article-title":"Targeted disruptions of the murine Hoxa-4 and Hoxa-6 genes result in homeotic transformations of components of the vertebral column","volume":"46","author":"Kostic","year":"1994","journal-title":"Mech. Dev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Coulombe, Y., Lemieux, M., Moreau, J., Aubin, J., Joksimovic, M., B\u00e9rub\u00e9-Simard, F.A., Tabari\u00e8s, S., Boucherat, O., Guillou, F., and Larochelle, C. (2010). Multiple promoters and alternative splicing: Hoxa5 transcriptional complexity in the mouse embryo. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0010600"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1006\/dbio.2002.0596","article-title":"Cooperation of Hoxa5 and Pax1 genes during formation of the pectoral girdle","volume":"244","author":"Aubin","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1006\/dbio.1997.8746","article-title":"Early postnatal lethality in Hoxa-5 mutant mice is attributable to respiratory tract defects","volume":"192","author":"Aubin","year":"1997","journal-title":"Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1152\/ajplung.00006.2013","article-title":"Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis","volume":"304","author":"Boucherat","year":"2013","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.2353\/ajpath.2006.051333","article-title":"Impact of the loss of Hoxa5 function on lung alveogenesis","volume":"169","author":"Mandeville","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1242\/bio.20121701","article-title":"The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways","volume":"1","author":"Boucherat","year":"2012","journal-title":"Biol. Open"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/nn.3242","article-title":"Sustained Hox5 gene activity is required for respiratory motor neuron development","volume":"15","author":"Philippidou","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1203\/01.PDR.0000139427.26083.3D","article-title":"Respiratory adaptations to lung morphological defects in adult mice lacking Hoxa5 gene function","volume":"56","author":"Kinkead","year":"2004","journal-title":"Pediatr. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.1242\/dev.129.17.4075","article-title":"Stomach regional specification requires Hoxa5-driven mesenchymal-epithelial signaling","volume":"129","author":"Aubin","year":"2002","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/ajpcell.1999.277.5.C965","article-title":"Loss of Hoxa5 gene function in mice perturbs intestinal maturation","volume":"277","author":"Aubin","year":"1999","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/dvdy.10325","article-title":"Perturbed thyroid morphology and transient hypothyroidism symptoms in Hoxa5 mutant mice","volume":"227","author":"Meunier","year":"2003","journal-title":"Dev. Dyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1002\/dvdy.20822","article-title":"Stromal Hoxa5 function controls the growth and differentiation of mammary alveolar epithelium","volume":"235","author":"Garin","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1210\/en.2011-1766","article-title":"The loss of Hoxa5 function causes estrous acyclicity and ovarian epithelial inclusion cysts","volume":"153","author":"Gendronneau","year":"2012","journal-title":"Endocrinology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/BF02981536","article-title":"Genetical studies on the skeleton of the mouse","volume":"52","year":"1954","journal-title":"J. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0092-8674(88)90039-6","article-title":"Undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1","volume":"55","author":"Balling","year":"1988","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1242\/dev.120.5.1109","article-title":"The role of Pax-1 in axial skeleton development","volume":"120","author":"Wallin","year":"1994","journal-title":"Development"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/8792","article-title":"Sox9 is required for cartilage formation","volume":"22","author":"Bi","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.mod.2013.02.002","article-title":"Hoxa-5 acts in segmented somites to regulate cervical vertebral morphology","volume":"130","author":"Chen","year":"2013","journal-title":"Mech. Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1101\/gad.9.1.108","article-title":"Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation","volume":"9","author":"Rancourt","year":"1995","journal-title":"Genes Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1242\/dev.007567","article-title":"Hox patterning of the vertebrate rib cage","volume":"134","author":"McIntyre","year":"2007","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.rcl.2008.11.009","article-title":"Congenital abnormalities of intrathoracic airways","volume":"47","author":"Desir","year":"2009","journal-title":"Radiol. Clin. North Am."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7058","DOI":"10.1073\/pnas.1007293108","article-title":"Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development","volume":"108","author":"Geng","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","first-page":"5671","article-title":"The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis","volume":"14","author":"Bohinski","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1152\/ajplung.1995.269.4.L429","article-title":"Transcription factors and pattern formation in the developing lung","volume":"269","author":"Cardoso","year":"1995","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/bdrc.20062","article-title":"Parabronchial smooth muscle cells and alveolar myofibroblasts in lung development","volume":"78","author":"Kim","year":"2006","journal-title":"Birth Defects Res. C. Embryo Today"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1172\/JCI29176","article-title":"SPDEF regulates goblet cell hyperplasia in the airway epithelium","volume":"117","author":"Park","year":"2007","journal-title":"J. Clin. Invest."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1164\/rccm.200811-1768OC","article-title":"Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma","volume":"180","author":"Park","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1242\/dev.00966","article-title":"Foxa2 regulates alveolarization and goblet cell hyperplasia","volume":"131","author":"Wan","year":"2004","journal-title":"Development"},{"key":"ref_47","first-page":"2914","article-title":"SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production","volume":"119","author":"Chen","year":"2009","journal-title":"J. Clin. Invest."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1242\/dev.029249","article-title":"Notch signaling promotes airway mucous metaplasia and inhibits alveolar development","volume":"136","author":"Guseh","year":"2009","journal-title":"Development"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.celrep.2015.07.020","article-title":"Hox5 genes regulate the Wnt2\/2b-Bmp4-signaling axis during lung development","volume":"12","author":"Hrycaj","year":"2015","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1242\/dev.109.2.329","article-title":"Mouse Hox-3.4: Homeobox sequence and embryonic expression patterns with other members of the Hox gene gen network","volume":"109","author":"Gaunt","year":"1990","journal-title":"Development"},{"key":"ref_51","first-page":"267","article-title":"The effect of spinal cord transection on lung development in fetal sheep","volume":"3","author":"Liggins","year":"1981","journal-title":"J. Dev. Physiol."},{"key":"ref_52","first-page":"1261","article-title":"The role of fetal breathing-like movements in lung organogenesis","volume":"20","author":"Inanlou","year":"2005","journal-title":"Histol. Histopathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0002-9440(10)64042-4","article-title":"HOX genes in human lung: Altered expression in primary pulmonary hypertension and emphysema","volume":"158","author":"Golpon","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1152\/physiolgenomics.00108.2007","article-title":"Gene expression profiling in lung fibroblasts reveals new players in alveolarization","volume":"32","author":"Boucherat","year":"2007","journal-title":"Physiol. Genomics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/1471-2407-12-348","article-title":"MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5","volume":"12","author":"Liu","year":"2012","journal-title":"BMC Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1183\/09031936.00145809","article-title":"Is COPD in adulthood really so far removed from early development?","volume":"35","author":"Shi","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0168-9525(99)01957-5","article-title":"Endoderm development: From patterning to organogenesis","volume":"16","author":"Melton","year":"2000","journal-title":"Trends Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1047>3.3.CO;2-Y","article-title":"Molecular mechanisms of development of the gastrointestinal tract","volume":"219","author":"Roberts","year":"2000","journal-title":"Dev. Dynam."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1002\/j.1460-2075.1987.tb02602.x","article-title":"Specific expression of the Hox 1.3 homeo box gene in murine embryonic structures originating from or induced by the mesoderm","volume":"6","author":"Dony","year":"1987","journal-title":"EMBO J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1016\/S0021-9258(18)49981-4","article-title":"Homeobox gene expression in the intestinal epithelium of adult mice","volume":"266","author":"James","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S1534-5807(01)00064-8","article-title":"Signaling pathways in mammary gland development","volume":"1","author":"Hennighausen","year":"2001","journal-title":"Dev. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0090-8258(92)90205-W","article-title":"Endosalpingiosis in association with ovarian surface papillary tumor of borderline malignancy","volume":"46","author":"Ryuko","year":"1992","journal-title":"Gynecol. Oncol."},{"key":"ref_63","first-page":"255","article-title":"Ovarian surface epithelium: Biology, endocrinology, and pathology","volume":"22","author":"Auersperg","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1530\/rep.0.1230743","article-title":"Roles of the ovarian surface epithelium in ovulation and carcinogenesis","volume":"123","author":"Murdoch","year":"2002","journal-title":"Reproduction"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0025-7125(16)30878-1","article-title":"The aging ovary","volume":"71","author":"Nicosia","year":"1987","journal-title":"Med. Clin. North Am."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/PGP.0b013e3181f45f3e","article-title":"The origin of ovarian carcinomas: A unifying hypothesis","volume":"30","author":"Auersperg","year":"2011","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1152\/ajpcell.00478.2005","article-title":"Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium","volume":"290","author":"Ahmed","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1182\/blood.V93.10.3391.410k26_3391_3400","article-title":"Characterization of HOX gene expression during myelopoiesis: Role of HOXA5 in lineage commitment and maturation","volume":"93","author":"Fuller","year":"1999","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1182\/blood.V94.2.519.414k20_519_528","article-title":"Constitutive HOXA5 expression inhibits erythropoiesis and increases myelopoiesis from human hematopoietic progenitors","volume":"94","author":"Crooks","year":"1999","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nrc907","article-title":"Deregulated homeobox gene expression in cancer: cause or consequence?","volume":"2","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2826","article-title":"The Hox genes and their roles in oncogenesis","volume":"10","author":"Shah","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7177","DOI":"10.1158\/0008-5472.CAN-04-1717","article-title":"Homeobox D10 induces phenotypic reversion of breast tumor cells in a three-dimensional culture model","volume":"65","author":"Carrio","year":"2005","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1089\/lrb.2005.3.240","article-title":"A role for HoxA5 in regulating angiogenesis and vascular patterning","volume":"3","author":"Rhoads","year":"2005","journal-title":"Lymphat. Res. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1158\/0008-5472.CAN-06-4283","article-title":"A role for the HOXB7 homeodomain protein in DNA repair","volume":"67","author":"Rubin","year":"2007","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1158\/0008-5472.CAN-07-2926","article-title":"Hoxb7 inhibits transgenic HER-2\/neu\u2013induced mouse mammary tumor onset but promotes progression and lung metastasis","volume":"68","author":"Chen","year":"2008","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0959-8049(97)00010-5","article-title":"Homeobox genes: Molecular link between congenital anomalies and cancer","volume":"33","author":"Anbazhagan","year":"1997","journal-title":"Eur. J. Cancer"},{"key":"ref_77","first-page":"305","article-title":"Expression pattern of a homeotic gene, HOXA5, in normal breast and in breast tumors","volume":"28","author":"Henderson","year":"2006","journal-title":"Cell. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/35016125","article-title":"Compromised HOXA5 function can limit p53 expression in human breast tumours","volume":"405","author":"Raman","year":"2000","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1074\/jbc.M411018200","article-title":"HOXA5-twist interaction alters p53 homeostasis in breast cancer cells","volume":"280","author":"Stasinopoulos","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1128\/MCB.24.2.924-935.2004","article-title":"HOXA5-induced apoptosis in breast cancer cells is mediated by caspases 2 and 8","volume":"24","author":"Chen","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1593\/neo.05766","article-title":"HOXA5 regulates hMLH1 expression in breast cancer cells","volume":"8","author":"Duriseti","year":"2006","journal-title":"Neoplasia"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"995","DOI":"10.2353\/ajpath.2010.090499","article-title":"Influence of Hoxa5 on p53 tumorigenic outcome in mice","volume":"176","author":"Gendronneau","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1093\/jnci\/88.24.1810","article-title":"Microscopic benign and invasive malignant neoplasms and a cancer-prone phenotype in prophylactic oophorectomies","volume":"88","author":"Salazar","year":"1996","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/BF01606911","article-title":"Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor receptor in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary","volume":"421","author":"Wang","year":"1992","journal-title":"Virchows Arch. A Pathol. Anat. Histopathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2559.1995.tb01528.x","article-title":"p53 protein expression in putative precursor lesions of epithelial ovarian cancer","volume":"27","author":"Hutson","year":"1995","journal-title":"Histopathology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/(SICI)1097-0215(19970620)74:3<275::AID-IJC7>3.0.CO;2-W","article-title":"E-cadherin expression in human epithelial ovarian cancer and normal ovary","volume":"74","author":"Sundfeldt","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/1097-0215(20000520)89:3<242::AID-IJC6>3.0.CO;2-6","article-title":"Lack of expression of c-KIT in ovarian cancers is associated with poor prognosis","volume":"89","author":"Tonary","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ygyno.2006.08.052","article-title":"Emerging roles for PAX8 in ovarian cancer and endosalpingeal development","volume":"104","author":"Bowen","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/path.2659","article-title":"Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma","volume":"220","author":"Madore","year":"2010","journal-title":"J. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1007\/s13277-014-2988-4","article-title":"HOXA5 indicates poor prognosis and suppresses cell proliferation by regulating p21 expression in non-small cell lung cancer","volume":"36","author":"Zhang","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/mc.20561","article-title":"Epigenetic inactivation of Homeobox A5 gene in non-small cell lung cancer and its relationship with clinicopathological features","volume":"48","author":"Kim","year":"2009","journal-title":"Mol. Carcinog."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.ccell.2015.11.001","article-title":"HOXA5 counteracts stem cell traits by inhibiting Wnt signaling in colorectal cancer","volume":"28","author":"Dafflon","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Cuevas, I., Layman, H., Coussens, L., and Boudreau, N. (2015). Sustained endothelial expression of HoxA5 in vivo impairs pathological angiogenesis and tumor progression. PloS ONE, 10.","DOI":"10.1371\/journal.pone.0121720"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1182\/blood-2007-07-104133","article-title":"Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5","volume":"111","author":"Chen","year":"2008","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1073\/pnas.93.10.4804","article-title":"The t (10; 11)(p13; q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family","volume":"93","author":"Dreyling","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/ncb1464","article-title":"Leukaemic transformation by CALM\u2013AF10 involves upregulation of Hoxa5 by hDOT1L","volume":"8","author":"Okada","year":"2006","journal-title":"Nat. Cell. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/10428190310001609942","article-title":"Expression of HOX genes in acute leukemia cell lines with and without MLL translocations","volume":"45","author":"Quentmeier","year":"2004","journal-title":"Leuk. Lymphoma"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"26551","DOI":"10.1074\/jbc.C000324200","article-title":"HOXA5 regulates expression of the progesterone receptor","volume":"275","author":"Raman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"19373","DOI":"10.1074\/jbc.M413528200","article-title":"Identification of transcriptional targets of HOXA5","volume":"280","author":"Chen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1101\/gad.10.18.2326","article-title":"In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries","volume":"10","author":"Chen","year":"1996","journal-title":"Genes Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1242\/dev.124.2.399","article-title":"In vivo functional analysis of the Hoxa-1 3\u2032 retinoic acid response element (3\u2032 RARE)","volume":"124","author":"Davenne","year":"1997","journal-title":"Development"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1093\/emboj\/16.14.4393","article-title":"Deletion of a HoxD enhancer induces transcriptional heterochrony leading to transposition of the sacrum","volume":"16","author":"Favier","year":"1997","journal-title":"EMBO J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1242\/dev.068346","article-title":"The regulation of Hox gene expression during animal development","volume":"140","author":"Mallo","year":"2013","journal-title":"Development"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.semcdb.2014.06.005","article-title":"Hox gene regulation and timing in embryogenesis","volume":"34","author":"Montavon","year":"2014","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1093\/emboj\/17.6.1788","article-title":"Selectivity, sharing and competitive interactions in the regulation of Hoxb genes","volume":"17","author":"Sharpe","year":"1998","journal-title":"EMBO J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0065-2660(07)00006-5","article-title":"Global control regions and regulatory landscapes in vertebrate development and evolution","volume":"61","author":"Spitz","year":"2008","journal-title":"Adv. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1101\/gad.292104","article-title":"Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription","volume":"18","author":"Chambeyron","year":"2004","journal-title":"Genes Dev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.cell.2009.02.006","article-title":"Evolution and functions of long noncoding RNAs","volume":"136","author":"Ponting","year":"2009","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.cell.2007.05.022","article-title":"Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs","volume":"129","author":"Rinn","year":"2007","journal-title":"Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1261\/rna.266707","article-title":"Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster","volume":"13","author":"Sessa","year":"2007","journal-title":"RNA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1242\/dev.108.3.435","article-title":"Position-specific activity of the Hox1.1 promoter in transgenic mice","volume":"108","author":"Balling","year":"1990","journal-title":"Development"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nature09819","article-title":"A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.celrep.2013.09.003","article-title":"Targeted disruption of Hotair leads to homeotic transformation and gene derepression","volume":"5","author":"Li","year":"2013","journal-title":"Cell Rep."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"B\u00e9rub\u00e9-Simard, F.A., Prudhomme, C., and Jeannotte, L. (2014). YY1 Acts as a Transcriptional Activator of Hoxa5. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093989"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/0896-6273(88)90167-5","article-title":"Spatial regulation of homeobox gene fusions in the embryonic central nervous system of transgenic mice","volume":"1","author":"Zakany","year":"1988","journal-title":"Neuron"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1101\/gad.4.2.180","article-title":"Region-specific enhancers near two mammalian homeo box genes define adjacent rostrocaudal domains in the central nervous system","volume":"4","author":"Tuggle","year":"1990","journal-title":"Genes Dev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1006\/dbio.1998.9189","article-title":"Hoxa5 gene regulation: A gradient of binding activity to a brachial spinal cord element","volume":"208","author":"Nowling","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/(SICI)1097-0177(199902)214:2<127::AID-AJA3>3.0.CO;2-F","article-title":"Multiple cis-acting regulatory regions are required for restricted spatio-temporal Hoxa5 gene expression","volume":"214","author":"Larochelle","year":"1999","journal-title":"Dev. Dyn."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1128\/MCB.25.4.1389-1401.2005","article-title":"Cdx protein interaction with Hoxa5 regulatory sequences contributes to Hoxa5 regional expression along the axial skeleton","volume":"25","author":"Lapointe","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/10425170290034507","article-title":"Sequence analysis of a Hoxa4-Hoxa5 intergenic region including shared regulatory elements","volume":"13","author":"Moreau","year":"2002","journal-title":"DNA Seq."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"24103","DOI":"10.1074\/jbc.M300774200","article-title":"The direct context of a Hox retinoic acid response element is crucial for its activity","volume":"278","author":"Oosterveen","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1242\/dev.125.11.1991","article-title":"Expression of the murine Hoxa4 gene requires both autoregulation and a conserved retinoic acid response element","volume":"125","author":"Packer","year":"1998","journal-title":"Development"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"8007","DOI":"10.1158\/0008-5472.CAN-07-1405","article-title":"HOXA5 acts directly downstream of retinoic acid receptor \u03b2 and contributes to retinoic acid\u2013induced apoptosis and growth inhibition","volume":"67","author":"Chen","year":"2007","journal-title":"Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4161\/trns.1.2.12375","article-title":"Yin Yang 1: A multifaceted protein beyond a transcription factor","volume":"1","author":"Deng","year":"2010","journal-title":"Transcription"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1242\/dev.120469","article-title":"Epithelial inactivation of Yy1 abrogates lung branching morphogenesis","volume":"142","author":"Boucherat","year":"2015","journal-title":"Development"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1242\/dev.02677","article-title":"Juxtaposed Polycomb complexes co-regulate vertebral identity","volume":"133","author":"Kim","year":"2006","journal-title":"Development"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0378111902010910","article-title":"Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development","volume":"302","author":"Hershko","year":"2003","journal-title":"Gene"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Mujahid, S., Nielsen, H.C., and Volpe, M.V. (2013). MiR-221 and miR-130a regulate lung airway and vascular development. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055911"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.cellsig.2013.03.015","article-title":"Retinoic acid-induced HOXA5 expression is co-regulated by HuR and miR-130a","volume":"25","author":"Yang","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"12580","DOI":"10.1038\/srep12580","article-title":"Induction of p53-independent apoptosis by ectopic expression of HOXA5 in human liposarcomas","volume":"5","author":"Lee","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.bbrc.2015.02.033","article-title":"miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5","volume":"458","author":"Wang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/mc.20043","article-title":"Increased DNA methylation in the HoxA5 promoter region correlates with decreased expression of the gene during tumor promotion","volume":"41","author":"Watson","year":"2004","journal-title":"Mol. Carcinog."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/carcin\/bgl133","article-title":"HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia","volume":"28","author":"Strathdee","year":"2006","journal-title":"Carcinogenesis"}],"container-title":["Journal of Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2221-3759\/4\/2\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:21:17Z","timestamp":1760210477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2221-3759\/4\/2\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,25]]},"references-count":133,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["jdb4020013"],"URL":"https:\/\/doi.org\/10.3390\/jdb4020013","relation":{},"ISSN":["2221-3759"],"issn-type":[{"value":"2221-3759","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,25]]}}}