{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:22:20Z","timestamp":1760239340571,"version":"build-2065373602"},"reference-count":104,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:00:00Z","timestamp":1604966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES) - Rede de Pesquisa em Gen\u00f4mica Populacional Humana","award":["Biocomputacional\/CAPES-051\/2013"],"award-info":[{"award-number":["Biocomputacional\/CAPES-051\/2013"]}]},{"name":"Funda\u00e7a\u0303o de Amparo a\u0300 Pesquisa do Estado do Rio Grande do Norte","award":["005\/2011"],"award-info":[{"award-number":["005\/2011"]}]},{"name":"Conselho Nacional de Desenvolvimento Cienti\u0301fico e Tecnolo\u0301gico (CNPq),","award":["306815\/2018-4 and 483031\/2013-5"],"award-info":[{"award-number":["306815\/2018-4 and 483031\/2013-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values &lt; 0.05 and |Log2(Fold-Change)| &gt; 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.<\/jats:p>","DOI":"10.3390\/cancers12113311","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T14:10:41Z","timestamp":1605017441000},"page":"3311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7446-6087","authenticated-orcid":false,"given":"Diego","family":"Marques","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"},{"name":"Laborat\u00f3rio de Bioan\u00e1lise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Av. Nilo Pe\u00e7anha, 620, Petr\u00f3polis, Natal 59012-300, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Layse Raynara","family":"Ferreira-Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioan\u00e1lise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Av. Nilo Pe\u00e7anha, 620, Petr\u00f3polis, Natal 59012-300, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenna Larissa","family":"Ferreira-Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioan\u00e1lise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Av. Nilo Pe\u00e7anha, 620, Petr\u00f3polis, Natal 59012-300, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Beatriz","family":"Bezerra-Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioan\u00e1lise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Av. Nilo Pe\u00e7anha, 620, Petr\u00f3polis, Natal 59012-300, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romualdo da Silva","family":"Correa","sequence":"additional","affiliation":[{"name":"Departamento de Cirurgia Oncol\u00f3gica, Liga Norte Riograndense Contra o C\u00e2ncer, R. M\u00e1rio Neg\u00f3cio, 2267, Quintas, Natal 59040-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Cesar de Oliveira","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Patologia e Citopatologia, Liga Norte Riograndense Contra o C\u00e2ncer, R. M\u00e1rio Neg\u00f3cio, 2267, Quintas, Natal 59040-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0189-0573","authenticated-orcid":false,"given":"Tatiana","family":"Vinasco-Sandoval","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-0126","authenticated-orcid":false,"given":"Katia de Paiva","family":"Lopes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3311-4197","authenticated-orcid":false,"given":"Ricardo Assun\u00e7\u00e3o","family":"Vialle","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4180-9925","authenticated-orcid":false,"given":"Amanda Ferreira","family":"Vidal","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9252-0278","authenticated-orcid":false,"given":"Vivian Nogueira","family":"Silbiger","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioan\u00e1lise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Av. Nilo Pe\u00e7anha, 620, Petr\u00f3polis, Natal 59012-300, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-1483","authenticated-orcid":false,"given":"\u00c2ndrea","family":"Ribeiro-dos-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana e M\u00e9dica, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Universidade Federal do Par\u00e1, Av. Augusto Corr\u00eaa, 01, Guam\u00e1, Bel\u00e9m 66.075-110, Brazil"},{"name":"N\u00facleo de Pesquisas em Oncologia, Universidade Federal do Par\u00e1, R. dos Mundurucus, 4487, Guam\u00e1, Bel\u00e9m 66073-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2018). Cancer Today, Global Cancer Observatory."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1159\/000320064","article-title":"The Use of Molecular Markers in the Diagnosis of Colorectal Cancer Screening","volume":"28","author":"Schmid","year":"2010","journal-title":"Dig. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.semcancer.2018.02.002","article-title":"Cancer Molecular Markers: A Guide to Cancer Detection and Management","volume":"52 Pt 1","author":"Nair","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"264","DOI":"10.14740\/gr1062w","article-title":"Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature","volume":"11","author":"Baran","year":"2018","journal-title":"Gastroenterol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.7150\/jca.32038","article-title":"Impact of Tumor Site on Lymph Node Status and Survival in Colon Cancer","volume":"10","author":"Xie","year":"2019","journal-title":"J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejca.2017.07.016","article-title":"Understanding the Role of Primary Tumour Localisation in Colorectal Cancer Treatment and Outcomes","volume":"84","author":"Stintzing","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15065","DOI":"10.1038\/nrdp.2015.65","article-title":"Colorectal Cancer","volume":"1","author":"Kuipers","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_9","first-page":"9","article-title":"The Molecular Characteristics of Colorectal Cancer: Implications for Diagnosis and Therapy","volume":"16","author":"Nguyen","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1053\/bega.2001.0279","article-title":"Molecular and Genetic Defects in Colorectal Tumorigenesis","volume":"16","author":"Tejpar","year":"2002","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA Therapeutics: Towards a New Era for the Management of Cancer and Other Diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.canlet.2017.04.007","article-title":"MicroRNAs as Cancer Therapeutics: A Step Closer to Clinical Application","volume":"407","author":"Voss","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fussey, J.M., Vaidya, B., Kim, D., Clark, J., Ellard, S., and Smith, J.A. (2019). The Role of Molecular Genetics in the Clinical Management of Sporadic Medullary Thyroid Carcinoma: A Systematic Review. Clin. Endocrinol. (Oxf.).","DOI":"10.1111\/cen.14060"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1261\/rna.2183803","article-title":"A Uniform System for MicroRNA Annotation","volume":"9","author":"Ambros","year":"2003","journal-title":"RNA"},{"key":"ref_15","first-page":"1093","article-title":"Biomarkers in Colorectal Cancer","volume":"36","author":"Yiu","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nrc3932","article-title":"MicroRNA Biogenesis Pathways in Cancer","volume":"15","author":"Lin","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1673-8527(09)60053-9","article-title":"The Role of MicroRNAs in Colorectal Cancer","volume":"37","author":"Liu","year":"2010","journal-title":"J. Genet. Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.2353\/ajpath.2010.100024","article-title":"MicroRNAs as Biomarkers in Colorectal Cancer","volume":"177","author":"Schee","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ribeiro-dos-Santos, \u00c2., Khayat, A.S., Silva, A., Alencar, D.O., Lobato, J., Luz, L., Pinheiro, D.G., Varuzza, L., Assump\u00e7\u00e3o, M., and Assump\u00e7\u00e3o, P. (2010). Ultra-Deep Sequencing Reveals the MicroRNA Expression Pattern of the Human Stomach. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013205"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Moreira, F.C., Assump\u00e7\u00e3o, M., Hamoy, I.G., Darnet, S., Burbano, R., Khayat, A., Gon\u00e7alves, A.N., Alencar, D.O., Cruz, A., and Magalh\u00e3es, L. (2014). MiRNA Expression Profile for the Human Gastric Antrum Region Using Ultra-Deep Sequencing. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092300"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"246","DOI":"10.6026\/97320630010246","article-title":"Identification of MiRNAs Expression Profile in Gastric Cancer Using Self-Organizing Maps (SOM)","volume":"10","author":"Gomes","year":"2014","journal-title":"Bioinformation"},{"key":"ref_22","first-page":"1","article-title":"High-Throughput Sequencing of MiRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers","volume":"9","author":"Darnet","year":"2015","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_23","first-page":"111","article-title":"High-Throughput MiRNA Sequencing Reveals a Field Effect in Gastric Cancer and Suggests an Epigenetic Network Mechanism","volume":"9","author":"Moreira","year":"2015","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.3748\/wjg.v22.i6.2060","article-title":"Hsa-MiR-29c and Hsa-MiR-135b Differential Expression as Potential Biomarker of Gastric Carcinogenesis","volume":"22","author":"Vidal","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lopes, C.B., Magalh\u00e3es, L.L., Te\u00f3filo, C.R., Alves, A.P.N.N., Montenegro, R.C., Negrini, M., and Ribeiro-Dos-Santos, \u00c2. (2018). Differential Expression of Hsa-MiR-221, Hsa-MiR-21, Hsa-MiR-135b, and Hsa-MiR-29c Suggests a Field Effect in Oral Cancer. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4631-z"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.7150\/jca.27457","article-title":"Epigenetic Field Cancerization in Gastric Cancer: MicroRNAs as Promising Biomarkers","volume":"10","author":"Pereira","year":"2019","journal-title":"J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3389\/fgene.2019.00592","article-title":"MiRNome Reveals New Insights Into the Molecular Biology of Field Cancerization in Gastric Cancer","volume":"10","author":"Pereira","year":"2019","journal-title":"Front. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrc.2017.102","article-title":"An Evolutionary Perspective on Field Cancerization","volume":"18","author":"Curtius","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Schee, K., Lorenz, S., Worren, M.M., G\u00fcnther, C.C., Holden, M., Hovig, E., Fodstad, \u00d8., Meza-Zepeda, L.A., and Flatmark, K. (2013). Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066165"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1002\/ijc.30902","article-title":"Different MiR-21-3p Isoforms and Their Different Features in Colorectal Cancer","volume":"141","author":"Jiao","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_31","unstructured":"IARC (2019). WHO Classification of Tumours of the Digestive System, John Wiley & Sons. [5th ed.]. WHO Classification of Tumours Editorial Board."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python Framework to Work with High-Throughput Sequencing Data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S0014-5793(02)02873-9","article-title":"Discriminant Analysis to Evaluate Clustering of Gene Expression Data","volume":"522","author":"Vulpe","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-Based Map of the Human Proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and Integrative Analysis of Large Gene Lists Using DAVID Bioinformatics Resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics Enrichment Tools: Paths toward the Comprehensive Functional Analysis of Large Gene Lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING V11: Protein-Protein Association Networks with Increased Coverage, Supporting Functional Discovery in Genome-Wide Experimental Datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6637","DOI":"10.1007\/s13277-015-4550-4","article-title":"MTUS1 and Its Targeting MiRNAs in Colorectal Carcinoma: Significant Associations","volume":"37","author":"Ozcan","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s10020-018-0034-5","article-title":"Overexpression of MiR-21-5p Promotes Proliferation and Invasion of Colon Adenocarcinoma Cells through Targeting CHL1","volume":"24","author":"Yu","year":"2018","journal-title":"Mol. Med."},{"key":"ref_43","first-page":"1000","article-title":"Integrated Analysis of Colorectal Cancer MicroRNA Datasets: Identification of MicroRNAs Associated with Tumor Development","volume":"10","author":"Falzone","year":"2018","journal-title":"Aging (Albany N. Y.)"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S575","DOI":"10.33549\/physiolres.933808","article-title":"Gender-Dependent Expression of Leading and Passenger Strand of MiR-21 and MiR-16 in Human Colorectal Cancer and Adjacent Colonic Tissues","volume":"66","author":"Hasakova","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e152","DOI":"10.1038\/ctg.2016.11","article-title":"Expression Profiles of MiRNA Subsets Distinguish Human Colorectal Carcinoma and Normal Colonic Mucosa","volume":"7","author":"Pellatt","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41389-017-0006-6","article-title":"MiR-215-5p Is a Tumor Suppressor in Colorectal Cancer Targeting EGFR Ligand Epiregulin and Its Transcriptional Inducer HOXB9","volume":"6","author":"Merhautova","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_47","first-page":"2013","article-title":"MicroRNA Expression Profiling in the Colorectal Normal-Adenoma-Carcinoma Transition","volume":"18","author":"Li","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_48","first-page":"2256","article-title":"MiR-338-3p Suppresses Colorectal Cancer Proliferation and Progression by Inhibiting MACC1","volume":"11","author":"Zou","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/jjco\/hyt181","article-title":"MicroRNA-338-3p Inhibits Colorectal Carcinoma Cell Invasion and Migration by Targeting Smoothened","volume":"44","author":"Xue","year":"2014","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.3760\/cma.j.issn.0366-6999.20140478","article-title":"Relationship between MiRNA-338-3p Expression and Progression and Prognosis of Human Colorectal Carcinoma","volume":"127","author":"Sun","year":"2014","journal-title":"Chin. Med. J. (Engl.)"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.ejca.2013.12.010","article-title":"Clinical and Biological Significance of MiR-378a-3p and MiR-378a-5p in Colorectal Cancer","volume":"50","author":"Li","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_52","first-page":"1159","article-title":"Screening MiRNAs for Early Diagnosis of Colorectal Cancer by Small RNA Deep Sequencing and Evaluation in a Chinese Patient Population","volume":"9","author":"Wang","year":"2016","journal-title":"Onco. Targets. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.2147\/OTT.S184118","article-title":"MicroRNA-143-3p Suppresses Tumorigenesis by Targeting Catenin-\u03941 in Colorectal Cancer","volume":"12","author":"Ding","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/cas.13910","article-title":"MicroRNA-143-3p Inhibits Colorectal Cancer Metastases by Targeting ITGA6 and ASAP3","volume":"110","author":"Guo","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"37544","DOI":"10.18632\/oncotarget.6065","article-title":"Clinical Value of Integrated-Signature MiRNAs in Colorectal Cancer: MiRNA Expression Profiling Analysis and Experimental Validation","volume":"6","author":"Chen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3727\/096504017X15004613574679","article-title":"MiR-133a-3p Targets SUMO-Specific Protease 1 to Inhibit Cell Proliferation and Cell Cycle Progress in Colorectal Cancer","volume":"26","author":"Zhou","year":"2018","journal-title":"Oncol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27256","DOI":"10.18632\/oncotarget.25535","article-title":"Extensive Screening of MicroRNA Populations Identifies Hsa-MiR-375 and Hsa-MiR-133a-3p as Selective Markers for Human Rectal and Colon Cancer","volume":"9","author":"Weber","year":"2018","journal-title":"Oncotarget"},{"key":"ref_58","first-page":"1494","article-title":"MiR-182-5p Inhibited Proliferation and Metastasis of Colorectal Cancer by Targeting MTDH","volume":"23","author":"Jin","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pizzini, S., Bisognin, A., Mandruzzato, S., Biasiolo, M., Facciolli, A., Perilli, L., Rossi, E., Esposito, G., Rugge, M., and Pilati, P. (2013). Impact of MicroRNAs on Regulatory Networks and Pathways in Human Colorectal Carcinogenesis and Development of Metastasis. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-589"},{"key":"ref_60","first-page":"1437","article-title":"MicroRNA MiR-125b Is a Prognostic Marker in Human Colorectal Cancer","volume":"38","author":"Nishida","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1756-8722-6-6","article-title":"Diverse Functions of MiR-125 Family in Different Cell Contexts","volume":"6","author":"Sun","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_62","first-page":"154","article-title":"Differential MicroRNA Epression in Asthma and the Role of MiR-1248 in Regulation of IL-5","volume":"1","author":"Panganiban","year":"2012","journal-title":"Am. J. Clin. Exp. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1158\/0008-5472.CAN-14-2379","article-title":"Interleukin-5 Facilitates Lung Metastasis by Modulating the Immune Microenvironment","volume":"75","author":"Zaynagetdinov","year":"2015","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and Cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and Cancer: Triggers, Mechanisms, and Consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1172\/JCI80004","article-title":"From Mice to Humans: Developments in Cancer Immunoediting","volume":"125","author":"Teng","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc1252","article-title":"Cytokines in Cancer Pathogenesis and Cancer Therapy","volume":"4","author":"Dranoff","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Almog, N., Ma, L., Schwager, C., Brinkmann, B.G., Beheshti, A., Vajkoczy, P., Folkman, J., Hlatky, L., and Abdollahi, A. (2012). Consensus Micro RNAs Governing the Switch of Dormant Tumors to the Fast-Growing Angiogenic Phenotype. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044001"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4161\/trns.25558","article-title":"Transcriptional Changes Induced by the Tumor Dormancy-Associated MicroRNA-190","volume":"4","author":"Almog","year":"2013","journal-title":"Transcription"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1158\/0008-5472.CAN-14-2394","article-title":"TWIST1-Induced MiR-424 Reversibly Drives Mesenchymal Programming While Inhibiting Tumor Initiation","volume":"75","author":"Drasin","year":"2015","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13000-016-0536-9","article-title":"MiR-424-5p Participates in Esophageal Squamous Cell Carcinoma Invasion and Metastasis via SMAD7 Pathway Mediated EMT","volume":"11","author":"Wang","year":"2016","journal-title":"Diagn. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1038\/srep06248","article-title":"MiR-424-5p Reversed Epithelial-Mesenchymal Transition of Anchorage-Independent HCC Cells by Directly Targeting ICAT and Suppressed HCC Progression","volume":"4","author":"Zhang","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.7150\/jca.20348","article-title":"Clinical Impact of MicroRNAs Associated With Cancer Stem Cells as a Prognostic Factor in Ovarian Carcinoma","volume":"8","author":"Cha","year":"2017","journal-title":"J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"75185","DOI":"10.18632\/oncotarget.12092","article-title":"MiR-424-5p Promotes Proliferation of Gastric Cancer by Targeting Smad3 through TGF-\u03b2 Signaling Pathway","volume":"7","author":"Wei","year":"2016","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s12253-013-9637-x","article-title":"MicroRNA-424-5p Suppresses the Expression of SOCS6 in Pancreatic Cancer","volume":"19","author":"Wu","year":"2013","journal-title":"Pathol. Oncol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-1-4419-6033-7_5","article-title":"Tgf-Beta Signaling Alterations and Colon Cancer","volume":"155","author":"Bellam","year":"2010","journal-title":"Cancer Treat. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11888-007-0001-y","article-title":"Mitotic Origins of Chromosomal Instability in Colorectal Cancer","volume":"3","author":"Dalton","year":"2007","journal-title":"Curr. Colorectal Cancer Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.3748\/wjg.v20.i8.1923","article-title":"Targeting Cell Death Signaling in Colorectal Cancer: Current Strategies and Future Perspectives","volume":"20","author":"Koehler","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1136\/gut.2004.052704","article-title":"Apoptosis and Colorectal Cancer","volume":"53","author":"Watson","year":"2004","journal-title":"Gut"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1177\/147323001103900631","article-title":"Let-7c MicroRNA Expression and Clinical Significance in Hepatocellular Carcinoma","volume":"39","author":"Zhu","year":"2011","journal-title":"J. Int. Med. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"F19","DOI":"10.1677\/ERC-09-0184","article-title":"The Role of Let-7 in Cell Differentiation and Cancer","volume":"17","author":"Boyerinas","year":"2010","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.3892\/ol.2017.5692","article-title":"MiR-215 Suppresses Proliferation and Migration of Non-Small Cell Lung Cancer Cells","volume":"13","author":"Cai","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/2211-5463.12733","article-title":"MiRNA-215-5p Suppresses the Aggressiveness of Breast Cancer Cells by Targeting Sox9","volume":"9","author":"Gao","year":"2019","journal-title":"FEBS Open Bio"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/jnen\/nlx036","article-title":"The Interplay of MicroRNAs in the Inflammatory Mechanisms Following Ischemic Stroke","volume":"76","author":"Khoshnam","year":"2017","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12967-019-1767-9","article-title":"MicroRNA-Regulated Pathways of Flow-Stimulated Angiogenesis and Vascular Remodeling in Vivo","volume":"17","author":"Henn","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1074\/jbc.M609383200","article-title":"Coordinate Suppression of ERBB2 and ERBB3 by Enforced Expression of Micro-RNA MiR-125a or MiR-125b","volume":"282","author":"Scott","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5062","DOI":"10.4049\/jimmunol.1102001","article-title":"MicroRNA-125b Potentiates Macrophage Activation","volume":"187","author":"Chaudhuri","year":"2011","journal-title":"J. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.3389\/fimmu.2019.01875","article-title":"The Two Faces of Tumor-Associated Macrophages and Their Clinical Significance in Colorectal Cancer","volume":"10","author":"Pinto","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_89","first-page":"1957","article-title":"MiR-378a-3p Inhibits Cellular Proliferation and Migration in Glioblastoma Multiforme by Targeting Tetraspanin 17","volume":"42","author":"Guo","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.3389\/fimmu.2019.02449","article-title":"Inhibition of MiR-378a-3p by Inflammation Enhances IL-33 Levels: A Novel Mechanism of Alarmin Modulation in Ulcerative Colitis","volume":"10","author":"Quera","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.2147\/OTT.S137433","article-title":"Role of Downregulated MiR-133a-3p Expression in Bladder Cancer: A Bioinformatics Study","volume":"10","author":"Gao","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e3101","DOI":"10.1038\/cddis.2017.493","article-title":"MiR-143 and MiR-145 Inhibit Gastric Cancer Cell Migration and Metastasis by Suppressing MYO6","volume":"8","author":"Lei","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12943-019-0954-x","article-title":"Targeting PI3K in Cancer: Mechanisms and Advances in Clinical Trials","volume":"18","author":"Yang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.ygeno.2018.05.006","article-title":"The P53-Signaling Pathway and Colorectal Cancer: Interactions between Downstream P53 Target Genes and MiRNAs","volume":"111","author":"Slattery","year":"2019","journal-title":"Genomics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"105","DOI":"10.5603\/FHC.a2015.0015","article-title":"The Hippo Pathway in Colorectal Cancer","volume":"53","author":"Wierzbicki","year":"2015","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_96","first-page":"4926","article-title":"Expression of Hippo Pathway Genes and Their Clinical Significance in Colon Adenocarcinoma","volume":"15","author":"Cho","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1158\/1078-0432.CCR-14-3300","article-title":"Molecular Pathways: Is AMPK a Friend or a Foe in Cancer?","volume":"21","author":"Hardie","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12943-019-0938-x","article-title":"The Forkhead-Box Family of Transcription Factors: Key Molecular Players in Colorectal Cancer Pathogenesis","volume":"18","author":"Laissue","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bbamcr.2014.11.007","article-title":"Role of the Focal Adhesion Protein TRIM15 in Colon Cancer Development","volume":"1853","author":"Lee","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jamcollsurg.2009.12.008","article-title":"Novel Expression Patterns of PI3K\/Akt\/MTOR Signaling Pathway Components in Colorectal Cancer","volume":"210","author":"Johnson","year":"2010","journal-title":"J. Am. Coll. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Itatani, Y., Kawada, K., and Sakai, Y. (2019). Transforming Growth Factor-\u03b2 Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235822"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1534735419862352","DOI":"10.1177\/1534735419862352","article-title":"Toward Normalization of the Tumor Microenvironment for Cancer Therapy","volume":"18","author":"Zheng","year":"2019","journal-title":"Integr. Cancer Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/s41467-017-01027-z","article-title":"Comprehensive Analysis of Normal Adjacent to Tumor Transcriptomes","volume":"8","author":"Aran","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1158\/1055-9965.EPI-14-0934","article-title":"Tumor Intrinsic Subtype Is Reflected in Cancer-Adjacent Tissue","volume":"24","author":"Sun","year":"2015","journal-title":"Cancer Epidemiol. Biomark. Prev."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/11\/3311\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:31:21Z","timestamp":1760178681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/11\/3311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,10]]},"references-count":104,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["cancers12113311"],"URL":"https:\/\/doi.org\/10.3390\/cancers12113311","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2020,11,10]]}}}