miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG
Accumulating evidence has suggested that microRNAs play important roles in the development of hepatocellular carcinoma (HCC) and are involved in drug resistance. miR-21-5p was overexpressed in a variety of cancers and promoted the tumorigenesis; however, the function of miR-21-5p in HCC still remain...
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| Veröffentlicht in: | DNA and cell biology 2019-08, Vol.38 (8), p.865-873 |
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| creator | Chen, Shifeng Yang, Chunyun Sun, Chengming Sun, Yong Yang, Zongjun Cheng, Shaoyun Zhuge, Baozhong |
| description | Accumulating evidence has suggested that microRNAs play important roles in the development of hepatocellular carcinoma (HCC) and are involved in drug resistance. miR-21-5p was overexpressed in a variety of cancers and promoted the tumorigenesis; however, the function of miR-21-5p in HCC still remains unknown. In this study, our results showed that miR-21-5p was highly expressed in HCC tissues and cell lines. Notably, the level of miR-21-5p was relatively higher in cisplatin (DDP)-resistant HCC patients. Overexpression of miR-21-5p attenuated the inhibitory effect of DDP on the proliferation and apoptosis of HCC cells. Mechanistically, the luciferase report assay-identified FAS ligand (FASLG) was a direct target of miR-21-5p. Overexpression of miR-21-5p decreased both the mRNA and protein levels of FASLG in HCC cells. FASLG was downregulated in HCC tissues and was significantly negatively correlated with the expression of miR-21-5p. Restoring the expression of FASLG upregulated the chemosensitivity of HCC cells expressing miR-21-5p. In conclusion, our results demonstrated that miR-21-5p targeted FASLG and suppressed the sensitivity of HCC cells to DDP treatment. |
| doi_str_mv | 10.1089/dna.2018.4529 |
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In this study, our results showed that miR-21-5p was highly expressed in HCC tissues and cell lines. Notably, the level of miR-21-5p was relatively higher in cisplatin (DDP)-resistant HCC patients. Overexpression of miR-21-5p attenuated the inhibitory effect of DDP on the proliferation and apoptosis of HCC cells. Mechanistically, the luciferase report assay-identified FAS ligand (FASLG) was a direct target of miR-21-5p. Overexpression of miR-21-5p decreased both the mRNA and protein levels of FASLG in HCC cells. FASLG was downregulated in HCC tissues and was significantly negatively correlated with the expression of miR-21-5p. Restoring the expression of FASLG upregulated the chemosensitivity of HCC cells expressing miR-21-5p. In conclusion, our results demonstrated that miR-21-5p targeted FASLG and suppressed the sensitivity of HCC cells to DDP treatment.</description><identifier>ISSN: 1044-5498</identifier><identifier>EISSN: 1557-7430</identifier><identifier>DOI: 10.1089/dna.2018.4529</identifier><identifier>PMID: 31225740</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Aged ; Animals ; Antineoplastic Agents - pharmacology ; Apoptosis ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - mortality ; Cell proliferation ; Cisplatin ; Cisplatin - pharmacology ; Disease-Free Survival ; Drug resistance ; Drug Resistance, Neoplasm - genetics ; Fas Ligand Protein - genetics ; Fas Ligand Protein - metabolism ; FasL protein ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Hepatocellular carcinoma ; Humans ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - genetics ; Liver Neoplasms - mortality ; Male ; Mice, Inbred BALB C ; MicroRNAs - genetics ; Middle Aged ; miRNA ; mRNA ; Sensitivity ; Tumorigenesis ; Xenograft Model Antitumor Assays</subject><ispartof>DNA and cell biology, 2019-08, Vol.38 (8), p.865-873</ispartof><rights>Copyright Mary Ann Liebert, Inc. Aug 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-4d4fa8c0bb045e19909e39ec19c84a271f7b3720e3924ad10ad218476ea531e63</citedby><cites>FETCH-LOGICAL-c387t-4d4fa8c0bb045e19909e39ec19c84a271f7b3720e3924ad10ad218476ea531e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31225740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Shifeng</creatorcontrib><creatorcontrib>Yang, Chunyun</creatorcontrib><creatorcontrib>Sun, Chengming</creatorcontrib><creatorcontrib>Sun, Yong</creatorcontrib><creatorcontrib>Yang, Zongjun</creatorcontrib><creatorcontrib>Cheng, Shaoyun</creatorcontrib><creatorcontrib>Zhuge, Baozhong</creatorcontrib><title>miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG</title><title>DNA and cell biology</title><addtitle>DNA Cell Biol</addtitle><description>Accumulating evidence has suggested that microRNAs play important roles in the development of hepatocellular carcinoma (HCC) and are involved in drug resistance. miR-21-5p was overexpressed in a variety of cancers and promoted the tumorigenesis; however, the function of miR-21-5p in HCC still remains unknown. In this study, our results showed that miR-21-5p was highly expressed in HCC tissues and cell lines. Notably, the level of miR-21-5p was relatively higher in cisplatin (DDP)-resistant HCC patients. Overexpression of miR-21-5p attenuated the inhibitory effect of DDP on the proliferation and apoptosis of HCC cells. Mechanistically, the luciferase report assay-identified FAS ligand (FASLG) was a direct target of miR-21-5p. Overexpression of miR-21-5p decreased both the mRNA and protein levels of FASLG in HCC cells. FASLG was downregulated in HCC tissues and was significantly negatively correlated with the expression of miR-21-5p. Restoring the expression of FASLG upregulated the chemosensitivity of HCC cells expressing miR-21-5p. In conclusion, our results demonstrated that miR-21-5p targeted FASLG and suppressed the sensitivity of HCC cells to DDP treatment.</description><subject>Aged</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Cell proliferation</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Disease-Free Survival</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Fas Ligand Protein - genetics</subject><subject>Fas Ligand Protein - metabolism</subject><subject>FasL protein</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - mortality</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>mRNA</subject><subject>Sensitivity</subject><subject>Tumorigenesis</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1044-5498</issn><issn>1557-7430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtLw0AUhQdRbH0s3cqAGzepd16ZZFmCLygItq7DJLnRKXk5kwj9906punB1D5ePw7n3EHLFYMEgSe-qziw4sGQhFU-PyJwppSMtBRwHDVJGSqbJjJx5vwUAxRmckplgnCstYU7q1r5GnEVqoOtpGBx6jxUdP5CusfN2tF923NG-pk84mLEvsWmmxjiaGVfarm8NzcLK07GnmfVDY0bb0WJHN8a9Y9Dv9GG5Xj1ekJPaNB4vf-Y5eXu432RP0erl8TlbrqJSJHqMZCVrk5RQFCAVsjSFFEWKJUvLRBquWa0LoTmEJZemYmAqzhKpYzRKMIzFObk9-A6u_5zQj3lr_T606bCffM65VLGQ4fSA3vxDt_3kupAuUHEiYq1BBio6UKXrvXdY54OzrXG7nEG-LyAPBeT7AvJ9AYG__nGdiharP_r34-IboV1_LA</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Chen, Shifeng</creator><creator>Yang, Chunyun</creator><creator>Sun, Chengming</creator><creator>Sun, Yong</creator><creator>Yang, Zongjun</creator><creator>Cheng, Shaoyun</creator><creator>Zhuge, Baozhong</creator><general>Mary Ann Liebert, Inc</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201908</creationdate><title>miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG</title><author>Chen, Shifeng ; Yang, Chunyun ; Sun, Chengming ; Sun, Yong ; Yang, Zongjun ; Cheng, Shaoyun ; Zhuge, Baozhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-4d4fa8c0bb045e19909e39ec19c84a271f7b3720e3924ad10ad218476ea531e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Cell proliferation</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Disease-Free Survival</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Fas Ligand Protein - genetics</topic><topic>Fas Ligand Protein - metabolism</topic><topic>FasL protein</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - mortality</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>mRNA</topic><topic>Sensitivity</topic><topic>Tumorigenesis</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Shifeng</creatorcontrib><creatorcontrib>Yang, Chunyun</creatorcontrib><creatorcontrib>Sun, Chengming</creatorcontrib><creatorcontrib>Sun, Yong</creatorcontrib><creatorcontrib>Yang, Zongjun</creatorcontrib><creatorcontrib>Cheng, Shaoyun</creatorcontrib><creatorcontrib>Zhuge, Baozhong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>DNA and cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Shifeng</au><au>Yang, Chunyun</au><au>Sun, Chengming</au><au>Sun, Yong</au><au>Yang, Zongjun</au><au>Cheng, Shaoyun</au><au>Zhuge, Baozhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG</atitle><jtitle>DNA and cell biology</jtitle><addtitle>DNA Cell Biol</addtitle><date>2019-08</date><risdate>2019</risdate><volume>38</volume><issue>8</issue><spage>865</spage><epage>873</epage><pages>865-873</pages><issn>1044-5498</issn><eissn>1557-7430</eissn><abstract>Accumulating evidence has suggested that microRNAs play important roles in the development of hepatocellular carcinoma (HCC) and are involved in drug resistance. miR-21-5p was overexpressed in a variety of cancers and promoted the tumorigenesis; however, the function of miR-21-5p in HCC still remains unknown. In this study, our results showed that miR-21-5p was highly expressed in HCC tissues and cell lines. Notably, the level of miR-21-5p was relatively higher in cisplatin (DDP)-resistant HCC patients. Overexpression of miR-21-5p attenuated the inhibitory effect of DDP on the proliferation and apoptosis of HCC cells. Mechanistically, the luciferase report assay-identified FAS ligand (FASLG) was a direct target of miR-21-5p. Overexpression of miR-21-5p decreased both the mRNA and protein levels of FASLG in HCC cells. FASLG was downregulated in HCC tissues and was significantly negatively correlated with the expression of miR-21-5p. Restoring the expression of FASLG upregulated the chemosensitivity of HCC cells expressing miR-21-5p. In conclusion, our results demonstrated that miR-21-5p targeted FASLG and suppressed the sensitivity of HCC cells to DDP treatment.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>31225740</pmid><doi>10.1089/dna.2018.4529</doi><tpages>9</tpages></addata></record> |
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| subjects | Aged Animals Antineoplastic Agents - pharmacology Apoptosis Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - mortality Cell proliferation Cisplatin Cisplatin - pharmacology Disease-Free Survival Drug resistance Drug Resistance, Neoplasm - genetics Fas Ligand Protein - genetics Fas Ligand Protein - metabolism FasL protein Female Gene Expression Regulation, Neoplastic - drug effects Hepatocellular carcinoma Humans Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - genetics Liver Neoplasms - mortality Male Mice, Inbred BALB C MicroRNAs - genetics Middle Aged miRNA mRNA Sensitivity Tumorigenesis Xenograft Model Antitumor Assays |
| title | miR-21-5p Suppressed the Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting FASLG |
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