miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma
MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using...
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| creator | Mei, Li-Li Wang, Wen-Jun Qiu, Yun-Tan Xie, Xiu-Feng Bai, Jie Shi, Zhi-Zhou |
| description | MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC. |
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Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0185636</identifier><identifier>PMID: 28968424</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Breast cancer ; Cancer genetics ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell cycle ; Cell Cycle - genetics ; Cell Line, Tumor ; Cell migration ; Cell Proliferation ; Collagenase 3 ; Colorectal cancer ; Development and progression ; DNA microarrays ; Down-Regulation ; E-cadherin ; Epithelial-Mesenchymal Transition - genetics ; Esophageal cancer ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - metabolism ; Esophageal Neoplasms - pathology ; Esophageal Squamous Cell Carcinoma ; Esophagus ; Gastric cancer ; Gelatinase A ; Gene Knockdown Techniques ; Genes, Tumor Suppressor ; HMGA2 Protein - genetics ; Human papillomavirus ; Humans ; Laboratories ; Lymphatic system ; Manufacturers ; Markers ; Matrilysin ; Medical diagnosis ; Medical prognosis ; Medical schools ; Medicine and Health Sciences ; Mesenchyme ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; N-Cadherin ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Ovarian cancer ; Real-Time Polymerase Chain Reaction ; Regulators ; Research and Analysis Methods ; Ribonucleic acid ; RNA ; Senescence ; Squamous cell carcinoma ; Stomach cancer ; Tissues ; Tumor suppressor genes</subject><ispartof>PloS one, 2017-10, Vol.12 (10), p.e0185636-e0185636</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Mei et al. 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Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Mei et al 2017 Mei et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c719t-79583f2a7382cb862f04810c9d3b87e92141d07d77866cebc1c067d89cf936083</citedby><cites>FETCH-LOGICAL-c719t-79583f2a7382cb862f04810c9d3b87e92141d07d77866cebc1c067d89cf936083</cites><orcidid>0000-0002-0967-375X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624607/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624607/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28968424$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mei, Li-Li</creatorcontrib><creatorcontrib>Wang, Wen-Jun</creatorcontrib><creatorcontrib>Qiu, Yun-Tan</creatorcontrib><creatorcontrib>Xie, Xiu-Feng</creatorcontrib><creatorcontrib>Bai, Jie</creatorcontrib><creatorcontrib>Shi, Zhi-Zhou</creatorcontrib><title>miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC.</description><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Cancer genetics</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Proliferation</subject><subject>Collagenase 3</subject><subject>Colorectal cancer</subject><subject>Development and progression</subject><subject>DNA microarrays</subject><subject>Down-Regulation</subject><subject>E-cadherin</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - 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Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Ovarian cancer</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Regulators</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Senescence</subject><subject>Squamous cell carcinoma</subject><subject>Stomach cancer</subject><subject>Tissues</subject><subject>Tumor suppressor 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functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma</title><author>Mei, Li-Li ; Wang, Wen-Jun ; Qiu, Yun-Tan ; Xie, Xiu-Feng ; Bai, Jie ; Shi, Zhi-Zhou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c719t-79583f2a7382cb862f04810c9d3b87e92141d07d77866cebc1c067d89cf936083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Cancer genetics</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Proliferation</topic><topic>Collagenase 3</topic><topic>Colorectal cancer</topic><topic>Development and progression</topic><topic>DNA microarrays</topic><topic>Down-Regulation</topic><topic>E-cadherin</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - metabolism</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophageal Squamous Cell Carcinoma</topic><topic>Esophagus</topic><topic>Gastric cancer</topic><topic>Gelatinase A</topic><topic>Gene Knockdown Techniques</topic><topic>Genes, Tumor Suppressor</topic><topic>HMGA2 Protein - genetics</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Laboratories</topic><topic>Lymphatic system</topic><topic>Manufacturers</topic><topic>Markers</topic><topic>Matrilysin</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Medical schools</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchyme</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mei, Li-Li</au><au>Wang, Wen-Jun</au><au>Qiu, Yun-Tan</au><au>Xie, Xiu-Feng</au><au>Bai, Jie</au><au>Shi, Zhi-Zhou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-10-02</date><risdate>2017</risdate><volume>12</volume><issue>10</issue><spage>e0185636</spage><epage>e0185636</epage><pages>e0185636-e0185636</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28968424</pmid><doi>10.1371/journal.pone.0185636</doi><tpages>e0185636</tpages><orcidid>https://orcid.org/0000-0002-0967-375X</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1945733201 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Biology and Life Sciences Breast cancer Cancer genetics Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell cycle Cell Cycle - genetics Cell Line, Tumor Cell migration Cell Proliferation Collagenase 3 Colorectal cancer Development and progression DNA microarrays Down-Regulation E-cadherin Epithelial-Mesenchymal Transition - genetics Esophageal cancer Esophageal Neoplasms - genetics Esophageal Neoplasms - metabolism Esophageal Neoplasms - pathology Esophageal Squamous Cell Carcinoma Esophagus Gastric cancer Gelatinase A Gene Knockdown Techniques Genes, Tumor Suppressor HMGA2 Protein - genetics Human papillomavirus Humans Laboratories Lymphatic system Manufacturers Markers Matrilysin Medical diagnosis Medical prognosis Medical schools Medicine and Health Sciences Mesenchyme Metastasis MicroRNA MicroRNAs MicroRNAs - genetics miRNA N-Cadherin Neoplasm Invasiveness Neoplasm Metastasis Ovarian cancer Real-Time Polymerase Chain Reaction Regulators Research and Analysis Methods Ribonucleic acid RNA Senescence Squamous cell carcinoma Stomach cancer Tissues Tumor suppressor genes |
| title | miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T14%3A46%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=miR-125b-5p%20functions%20as%20a%20tumor%20suppressor%20gene%20partially%20by%20regulating%20HMGA2%20in%20esophageal%20squamous%20cell%20carcinoma&rft.jtitle=PloS%20one&rft.au=Mei,%20Li-Li&rft.date=2017-10-02&rft.volume=12&rft.issue=10&rft.spage=e0185636&rft.epage=e0185636&rft.pages=e0185636-e0185636&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0185636&rft_dat=%3Cgale_plos_%3EA507748826%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1945733201&rft_id=info:pmid/28968424&rft_galeid=A507748826&rft_doaj_id=oai_doaj_org_article_ff36f40e78014ba4846c4eb7c28d1df1&rfr_iscdi=true |