miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells
MicroRNAs (miRNAs) have been shown to play essential roles in regulating the activity of human hepatocellular carcinoma (HCC) cells, thereby contributing to the suppression of invasion and metastasis. In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently...
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Veröffentlicht in: | Tumor biology 2016, Vol.37 (1), p.847-855 |
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creator | Wang, Lumin Yao, Jiayi Sun, Hongfei Sun, Reifang Chang, Su’e Yang, Yang Song, Tusheng Huang, Chen |
description | MicroRNAs (miRNAs) have been shown to play essential roles in regulating the activity of human hepatocellular carcinoma (HCC) cells, thereby contributing to the suppression of invasion and metastasis. In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently down-regulated in clinical HCC specimens, as compared with 15 corresponding adjacent normal tissues. Overexpression of miR-302b suppressed HCC cell invasion and metastasis. Regulation of NF-κB and matrix metalloproteinase (MMP)-2 expression by miR-302b was mediated via AKT2 in SMMC-7721 cells. Silencing AKT2 produced effects similar to those of miR-302b overexpression, which included inhibiting SMMC-7721 cell invasion and metastasis and dereasing NF-κB and MMP-2 expression. Furthermore, overexpression of AKT2 attenuated the effects of miR-302b overexpression. Taken together, our findings indicate that miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2, suggesting that miR-302b might represent a potential therapeutic target for HCC intervention. |
doi_str_mv | 10.1007/s13277-015-3330-5 |
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In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently down-regulated in clinical HCC specimens, as compared with 15 corresponding adjacent normal tissues. Overexpression of miR-302b suppressed HCC cell invasion and metastasis. Regulation of NF-κB and matrix metalloproteinase (MMP)-2 expression by miR-302b was mediated via AKT2 in SMMC-7721 cells. Silencing AKT2 produced effects similar to those of miR-302b overexpression, which included inhibiting SMMC-7721 cell invasion and metastasis and dereasing NF-κB and MMP-2 expression. Furthermore, overexpression of AKT2 attenuated the effects of miR-302b overexpression. Taken together, our findings indicate that miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2, suggesting that miR-302b might represent a potential therapeutic target for HCC intervention.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-015-3330-5</identifier><identifier>PMID: 26254095</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>3' Untranslated Regions ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Hepatocellular - embryology ; Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; HEK293 Cells ; Humans ; Immunohistochemistry ; Liver cancer ; Liver Neoplasms - metabolism ; Matrix Metalloproteinase 2 - metabolism ; Metastasis ; MicroRNAs ; MicroRNAs - metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; NF-kappa B - metabolism ; NF-kappa B p50 Subunit - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Research Article</subject><ispartof>Tumor biology, 2016, Vol.37 (1), p.847-855</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2015</rights><rights>International Society of Oncology and BioMarkers (ISOBM) 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-1ac3ff1c9407d97e046a0eab43abc822381bbdfc0e6455e8a316c8d1e8eba01c3</citedby><cites>FETCH-LOGICAL-c372t-1ac3ff1c9407d97e046a0eab43abc822381bbdfc0e6455e8a316c8d1e8eba01c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13277-015-3330-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-015-3330-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26254095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Lumin</creatorcontrib><creatorcontrib>Yao, Jiayi</creatorcontrib><creatorcontrib>Sun, Hongfei</creatorcontrib><creatorcontrib>Sun, Reifang</creatorcontrib><creatorcontrib>Chang, Su’e</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Song, Tusheng</creatorcontrib><creatorcontrib>Huang, Chen</creatorcontrib><title>miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>MicroRNAs (miRNAs) have been shown to play essential roles in regulating the activity of human hepatocellular carcinoma (HCC) cells, thereby contributing to the suppression of invasion and metastasis. In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently down-regulated in clinical HCC specimens, as compared with 15 corresponding adjacent normal tissues. Overexpression of miR-302b suppressed HCC cell invasion and metastasis. Regulation of NF-κB and matrix metalloproteinase (MMP)-2 expression by miR-302b was mediated via AKT2 in SMMC-7721 cells. Silencing AKT2 produced effects similar to those of miR-302b overexpression, which included inhibiting SMMC-7721 cell invasion and metastasis and dereasing NF-κB and MMP-2 expression. Furthermore, overexpression of AKT2 attenuated the effects of miR-302b overexpression. Taken together, our findings indicate that miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2, suggesting that miR-302b might represent a potential therapeutic target for HCC intervention.</description><subject>3' Untranslated Regions</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Hepatocellular - embryology</subject><subject>Cell Line, Tumor</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Silencing</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - metabolism</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Metastasis</subject><subject>MicroRNAs</subject><subject>MicroRNAs - metabolism</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>NF-kappa B - metabolism</subject><subject>NF-kappa B p50 Subunit - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Research Article</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUuLFTEQhYMozjj6A9xIwI2baFXSz-UwjA8cEGRch-p09bWHfpnqFu6_Nz13FBGEIhXId04VOUq9RHiLAOU7QWfL0gDmxjkHJn-kzjGzzoCr4HG6A4LJbOXO1DORO0hgXRdP1ZktbJ5BnZ8rGfuvxoFttGzLElmERQceBt1PP0n6edI0tXrklSRVL7o56raPHNbhqFeKB1776aAvP9_aJNHft5HSyQut826zDRR1oBj6aR7p3lmeqycdDcIvHvqF-vb--vbqo7n58uHT1eWNCa60q0EKrusw1BmUbV0yZAUBU5M5akJlrauwadouABdZnnNFDotQtcgVNwQY3IV6c_Jd4vxjY1n92Mu-AU08b-KxrFyNaAuX0Nf_oHfzFqe03T1VFA4xTxSeqBBnkcidX2I_Ujx6BL8n4k-J-PTRfk_E75pXD85bM3L7R_E7ggTYEyDpaTpw_Gv0f11_Ad-4lus</recordid><startdate>2016</startdate><enddate>2016</enddate><creator>Wang, Lumin</creator><creator>Yao, Jiayi</creator><creator>Sun, Hongfei</creator><creator>Sun, Reifang</creator><creator>Chang, Su’e</creator><creator>Yang, Yang</creator><creator>Song, Tusheng</creator><creator>Huang, Chen</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>2016</creationdate><title>miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells</title><author>Wang, Lumin ; Yao, Jiayi ; Sun, Hongfei ; Sun, Reifang ; Chang, Su’e ; Yang, Yang ; Song, Tusheng ; Huang, Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-1ac3ff1c9407d97e046a0eab43abc822381bbdfc0e6455e8a316c8d1e8eba01c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3' Untranslated Regions</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Hepatocellular - embryology</topic><topic>Cell Line, Tumor</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Silencing</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - metabolism</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Metastasis</topic><topic>MicroRNAs</topic><topic>MicroRNAs - metabolism</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>NF-kappa B - metabolism</topic><topic>NF-kappa B p50 Subunit - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Research Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Lumin</creatorcontrib><creatorcontrib>Yao, Jiayi</creatorcontrib><creatorcontrib>Sun, Hongfei</creatorcontrib><creatorcontrib>Sun, Reifang</creatorcontrib><creatorcontrib>Chang, Su’e</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Song, Tusheng</creatorcontrib><creatorcontrib>Huang, Chen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Lumin</au><au>Yao, Jiayi</au><au>Sun, Hongfei</au><au>Sun, Reifang</au><au>Chang, Su’e</au><au>Yang, Yang</au><au>Song, Tusheng</au><au>Huang, Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2016</date><risdate>2016</risdate><volume>37</volume><issue>1</issue><spage>847</spage><epage>855</epage><pages>847-855</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>MicroRNAs (miRNAs) have been shown to play essential roles in regulating the activity of human hepatocellular carcinoma (HCC) cells, thereby contributing to the suppression of invasion and metastasis. In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently down-regulated in clinical HCC specimens, as compared with 15 corresponding adjacent normal tissues. Overexpression of miR-302b suppressed HCC cell invasion and metastasis. Regulation of NF-κB and matrix metalloproteinase (MMP)-2 expression by miR-302b was mediated via AKT2 in SMMC-7721 cells. Silencing AKT2 produced effects similar to those of miR-302b overexpression, which included inhibiting SMMC-7721 cell invasion and metastasis and dereasing NF-κB and MMP-2 expression. Furthermore, overexpression of AKT2 attenuated the effects of miR-302b overexpression. Taken together, our findings indicate that miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2, suggesting that miR-302b might represent a potential therapeutic target for HCC intervention.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26254095</pmid><doi>10.1007/s13277-015-3330-5</doi><tpages>9</tpages></addata></record> |
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subjects | 3' Untranslated Regions Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Hepatocellular - embryology Cell Line, Tumor Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Silencing HEK293 Cells Humans Immunohistochemistry Liver cancer Liver Neoplasms - metabolism Matrix Metalloproteinase 2 - metabolism Metastasis MicroRNAs MicroRNAs - metabolism Neoplasm Invasiveness Neoplasm Metastasis NF-kappa B - metabolism NF-kappa B p50 Subunit - metabolism Proto-Oncogene Proteins c-akt - metabolism Research Article |
title | miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells |
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