{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:37:58Z","timestamp":1788273478079,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Life"],"abstract":"<jats:p>HMGA1 is a chromatin-binding protein and performs its biological function by remodeling chromatin structure or recruiting other transcription factors. However, the role of abnormally high level of HMGA1 in cancer cells and its regulatory mechanism still require further investigation. In this study, we performed a prognostic analysis and showed that high level of either HMGA1 or FOXM1 was associated with poor prognosis in various cancers based on the TCGA database. Furthermore, the expression pattern of HMGA1 and FOXM1 showed a significant strong positive correlation in most type of cancers, especially lung adenocarcinoma, pancreatic cancer and liver cancer. Further analysis of the biological effects of their high correlation in cancers suggested that cell cycle was the most significant related pathway commonly regulated by HMGA1 and FOXM1. After knockdown of HMGA1 and FOXM1 by specific siRNAs, an obvious increased G2\/M phase was observed in the siHMGA1 and siFOXM1 groups compared to the siNC group. The expression levels of key G2\/M phase regulatory genes PLK1 and CCNB1 were significantly downregulated. Importantly, HMGA1 and FOXM1 were identified to form a protein complex and co-located in the nucleus based on co-immunoprecipitation and immunofluorescence staining, respectively. Thus, our results provide the basic evidence that HMGA1 and FOXM1 cooperatively accelerate cell cycle progression by up-regulating PLK1 and CCNB1 to promote cancer cell proliferation.<\/jats:p>","DOI":"10.3390\/life13051225","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T05:04:44Z","timestamp":1684731884000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["HMGA1 and FOXM1 Cooperate to Promote G2\/M Cell Cycle Progression in Cancer Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Qingfang","family":"Zheng","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazhou","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Lei","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5945","authenticated-orcid":false,"given":"Yang","family":"Xi","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"188620","DOI":"10.1016\/j.bbcan.2021.188620","article-title":"The transcriptional stress response and its implications in cancer treatment","volume":"1876","author":"Zurita","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/s41591-018-0158-8","article-title":"Transcriptional addiction in cancer cells is mediated by YAP\/TAZ through BRD4","volume":"24","author":"Zanconato","year":"2018","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.cell.2016.12.013","article-title":"Transcriptional Addiction in Cancer","volume":"168","author":"Bradner","year":"2017","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1158\/0008-5472.CAN-06-4325","article-title":"Transcriptional control of the human high mobility group A1 gene: Basal and oncogenic Ras-regulated expression","volume":"67","author":"Cleynen","year":"2007","journal-title":"Cancer Res."},{"key":"ref_6","first-page":"2439","article-title":"High level expression of the HMGI (Y) gene during embryonic development","volume":"13","author":"Chiappetta","year":"1996","journal-title":"Oncogene"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Barh, D., Jain, N., Tiwari, S., Field, J.K., Padin-Iruegas, E., Ruibal, A., Lopez, R., Herranz, M., Bhattacharya, A., and Juneja, L. (2013). A novel in silico reverse-transcriptomics-based identification and blood-based validation of a panel of sub-type specific biomarkers in lung cancer. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-S6-S5"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.7150\/ijbs.72952","article-title":"High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential","volume":"18","author":"Wang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31714","DOI":"10.1038\/srep31714","article-title":"Function of high-mobility group A proteins in the DNA damage signaling for the induction of apoptosis","volume":"6","author":"Fujikane","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pellarin, I., Arnoldo, L., Costantini, S., Pegoraro, S., Ros, G., Penzo, C., Triolo, G., Demarchi, F., Sgarra, R., and Vindigni, A. (2016). The Architectural Chromatin Factor High Mobility Group A1 Enhances DNA Ligase IV Activity Influencing DNA Repair. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164258"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41419-018-0683-x","article-title":"HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration\/invasion via targeting miR-221\/222 in cervical cancer","volume":"9","author":"Fu","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.1097\/CAD.0000000000001201","article-title":"HMGA1 promotes hepatocellular carcinoma proliferation, migration, and regulates cell cycle via miR-195-5p","volume":"33","author":"Shi","year":"2022","journal-title":"Anticancer Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1517\/14728222.2014.900045","article-title":"The high mobility group A1 molecular switch: Turning on cancer-can we turn it off?","volume":"18","author":"Huso","year":"2014","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1073\/pnas.91.24.11318","article-title":"The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms","volume":"91","author":"Du","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.semcancer.2014.07.008","article-title":"FOXM1: A key oncofoetal transcription factor in health and disease","volume":"29","author":"Bella","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.semcancer.2017.08.009","article-title":"FoxM1: Repurposing an oncogene as a biomarker","volume":"52","author":"Nandi","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_17","first-page":"6860","article-title":"The TGFbeta1-FOXM1-HMGA1-TGFbeta1 positive feedback loop increases the cisplatin resistance of non-small cell lung cancer by inducing G6PD expression","volume":"11","author":"Zhang","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/ncb1217","article-title":"FoxM1 is required for execution of the mitotic programme and chromosome stability","volume":"7","author":"Laoukili","year":"2005","journal-title":"Nat. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.gene.2018.08.037","article-title":"LncRNA GACAT3 acts as a competing endogenous RNA of HMGA1 and alleviates cucurbitacin B-induced apoptosis of gastric cancer cells","volume":"678","author":"Lin","year":"2018","journal-title":"Gene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1158\/1078-0432.CCR-13-2311","article-title":"FOXM1c promotes pancreatic cancer epithelial-to-mesenchymal transition and metastasis via upregulation of expression of the urokinase plasminogen activator system","volume":"20","author":"Huang","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.gde.2016.12.007","article-title":"Combinatorial function of transcription factors and cofactors","volume":"43","author":"Reiter","year":"2017","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrg3207","article-title":"Transcription factors: From enhancer binding to developmental control","volume":"13","author":"Spitz","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1158\/0008-5472.CAN-17-3045","article-title":"Lessons from the Crypt: HMGA1-Amping up Wnt for Stem Cells and Tumor Progression","volume":"78","author":"Resar","year":"2018","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1126\/science.293.5532.1133","article-title":"Coordination of a transcriptional switch by HMGI(Y) acetylation","volume":"293","author":"Munshi","year":"2001","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e24192","DOI":"10.1002\/jcla.24192","article-title":"LINC00152 acts as a competing endogenous RNA of HMGA1 to promote the growth of gastric cancer cells","volume":"36","author":"Chen","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"763","DOI":"10.21037\/tcr.2019.12.10","article-title":"High-mobility group A1 (HMGA1) gene expressions in various colorectal cancer cell lines and correlation with prognosis","volume":"9","author":"Liu","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1101\/SQB.1993.058.01.011","article-title":"The high mobility group protein HMG I(Y) is an essential structural component of a virus-inducible enhancer complex","volume":"58","author":"Thanos","year":"1993","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12964-018-0266-6","article-title":"Regulation of the master regulator FOXM1 in cancer","volume":"16","author":"Liao","year":"2018","journal-title":"Cell Commun. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/ncb1767","article-title":"Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression","volume":"10","author":"Fu","year":"2008","journal-title":"Nat. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1038\/s41467-019-11162-4","article-title":"circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1","volume":"10","author":"Cheng","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.1038\/s41388-021-01895-2","article-title":"FOXM1 is required for small cell lung cancer tumorigenesis and associated with poor clinical prognosis","volume":"40","author":"Liang","year":"2021","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.aap9346","article-title":"An intrinsic S\/G(2) checkpoint enforced by ATR","volume":"361","author":"Saldivar","year":"2018","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/onc.2016.268","article-title":"FBXO31 protects against genomic instability by capping FOXM1 levels at the G2\/M transition","volume":"36","author":"Jeffery","year":"2017","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1186\/s13046-019-1307-8","article-title":"HMGA1 promotes breast cancer angiogenesis supporting the stability, nuclear localization and transcriptional activity of FOXM1","volume":"38","author":"Zanin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1016\/j.celrep.2019.02.054","article-title":"FOXM1 Deubiquitination by USP21 Regulates Cell Cycle Progression and Paclitaxel Sensitivity in Basal-like Breast Cancer","volume":"26","author":"Arceci","year":"2019","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/1873-3468.12071","article-title":"F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1","volume":"590","author":"Li","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17342","DOI":"10.18632\/oncotarget.3944","article-title":"Deregulation of HMGA1 expression induces chromosome instability through regulation of spindle assembly checkpoint genes","volume":"6","author":"Pierantoni","year":"2015","journal-title":"Oncotarget"}],"updated-by":[{"DOI":"10.3390\/life15111694","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000}}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/5\/1225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:35:24Z","timestamp":1761896124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/5\/1225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["life13051225"],"URL":"https:\/\/doi.org\/10.3390\/life13051225","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,22]]}}}