The miR‐140‐5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma
Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological func...
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| Veröffentlicht in: | The FASEB journal 2020-08, Vol.34 (8), p.10623-10639 |
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| creator | Huang, Chenchen Li, Jianfa Zhang, Xiaoting Xiong, Tiefu Ye, Jing Yu, Jing Gui, Yaoting |
| description | Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR‐140‐5p was upregulated in RCC tissues, whereas Krüppel‐like factor 9 (KLF9) was downregulated and correlated inversely with miR‐140‐5p in RCC tissues. miR‐140‐5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR‐140‐5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR‐140‐5p significantly suppressed the expression of KLF9 by binding to the 3ʹ‐UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv7.1 and KvLQT1) expression by binding to the site (−841/−827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR‐140‐5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies. |
| doi_str_mv | 10.1096/fj.202000088RR |
| format | Article |
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Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR‐140‐5p was upregulated in RCC tissues, whereas Krüppel‐like factor 9 (KLF9) was downregulated and correlated inversely with miR‐140‐5p in RCC tissues. miR‐140‐5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR‐140‐5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR‐140‐5p significantly suppressed the expression of KLF9 by binding to the 3ʹ‐UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv7.1 and KvLQT1) expression by binding to the site (−841/−827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR‐140‐5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.202000088RR</identifier><identifier>PMID: 32596959</identifier><language>eng</language><publisher>United States</publisher><subject>3' Untranslated Regions - genetics ; Animals ; Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - pathology ; Cell Line ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Disease Progression ; Down-Regulation - genetics ; Female ; Gene Expression Regulation, Neoplastic - genetics ; Genes, Tumor Suppressor - physiology ; HEK293 Cells ; Humans ; KCNQ1 ; KCNQ1 Potassium Channel - genetics ; Kidney Neoplasms - genetics ; Kidney Neoplasms - pathology ; KLF9 ; Kruppel-Like Transcription Factors - genetics ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs - genetics ; Middle Aged ; miR‐140‐5p ; proliferation/invasion/metastasis ; renal cell carcinoma ; Up-Regulation - genetics</subject><ispartof>The FASEB journal, 2020-08, Vol.34 (8), p.10623-10639</ispartof><rights>2020 Federation of American Societies for Experimental Biology</rights><rights>2020 Federation of American Societies for Experimental Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3812-dc561c2d464587030ceda016fd5c6224e08747a6e0d3fbd65778ca9fed280f033</citedby><cites>FETCH-LOGICAL-c3812-dc561c2d464587030ceda016fd5c6224e08747a6e0d3fbd65778ca9fed280f033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.202000088RR$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.202000088RR$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32596959$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Chenchen</creatorcontrib><creatorcontrib>Li, Jianfa</creatorcontrib><creatorcontrib>Zhang, Xiaoting</creatorcontrib><creatorcontrib>Xiong, Tiefu</creatorcontrib><creatorcontrib>Ye, Jing</creatorcontrib><creatorcontrib>Yu, Jing</creatorcontrib><creatorcontrib>Gui, Yaoting</creatorcontrib><title>The miR‐140‐5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR‐140‐5p was upregulated in RCC tissues, whereas Krüppel‐like factor 9 (KLF9) was downregulated and correlated inversely with miR‐140‐5p in RCC tissues. miR‐140‐5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR‐140‐5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR‐140‐5p significantly suppressed the expression of KLF9 by binding to the 3ʹ‐UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv7.1 and KvLQT1) expression by binding to the site (−841/−827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR‐140‐5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies.</description><subject>3' Untranslated Regions - genetics</subject><subject>Animals</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Disease Progression</subject><subject>Down-Regulation - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>KCNQ1</subject><subject>KCNQ1 Potassium Channel - genetics</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - pathology</subject><subject>KLF9</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miR‐140‐5p</subject><subject>proliferation/invasion/metastasis</subject><subject>renal cell carcinoma</subject><subject>Up-Regulation - genetics</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1OAjEUhRujEfzZujSzdDNw205_ZqlE1EA0Aq6b0ml1yAyDLUTZ-Qg-o09iCWjceRfn5ibfPTk5CJ1h6GDIedfNOgQIxJFyNNpDbcwopFxy2EdtkDlJOaeyhY5CmEUIA-aHqEUJy3nO8jYaT15sUpejr49PnEFUtugOhv28O-jdP-JEv5chWfimbpY2JMvIxuPZ2xDKZp40LvF2rqvE2CqK9qacN7U-QQdOV8Ge7vYxeupfT3q36fDh5q53OUwNlZikhWEcG1JkPGNSAAVjCx3zuYIZTkhmQYpMaG6hoG5acCaENDp3tiASHFB6jC62vjHT68qGparLsImi57ZZBUUyLAURjMiIdrao8U0I3jq18GWt_VphUJsilZupP0XGh_Od92pa2-IX_2kuAmwLvJWVXf9jp_rjK0JAEEK_AZGwffU</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Huang, Chenchen</creator><creator>Li, Jianfa</creator><creator>Zhang, Xiaoting</creator><creator>Xiong, Tiefu</creator><creator>Ye, Jing</creator><creator>Yu, Jing</creator><creator>Gui, Yaoting</creator><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>7X8</scope></search><sort><creationdate>202008</creationdate><title>The miR‐140‐5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma</title><author>Huang, Chenchen ; Li, Jianfa ; Zhang, Xiaoting ; Xiong, Tiefu ; Ye, Jing ; Yu, Jing ; Gui, Yaoting</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3812-dc561c2d464587030ceda016fd5c6224e08747a6e0d3fbd65778ca9fed280f033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>3' Untranslated Regions - genetics</topic><topic>Animals</topic><topic>Carcinoma, Renal Cell - genetics</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Disease Progression</topic><topic>Down-Regulation - genetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>KCNQ1</topic><topic>KCNQ1 Potassium Channel - genetics</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - pathology</topic><topic>KLF9</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miR‐140‐5p</topic><topic>proliferation/invasion/metastasis</topic><topic>renal cell carcinoma</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Chenchen</creatorcontrib><creatorcontrib>Li, Jianfa</creatorcontrib><creatorcontrib>Zhang, Xiaoting</creatorcontrib><creatorcontrib>Xiong, Tiefu</creatorcontrib><creatorcontrib>Ye, Jing</creatorcontrib><creatorcontrib>Yu, Jing</creatorcontrib><creatorcontrib>Gui, Yaoting</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Chenchen</au><au>Li, Jianfa</au><au>Zhang, Xiaoting</au><au>Xiong, Tiefu</au><au>Ye, Jing</au><au>Yu, Jing</au><au>Gui, Yaoting</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The miR‐140‐5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2020-08</date><risdate>2020</risdate><volume>34</volume><issue>8</issue><spage>10623</spage><epage>10639</epage><pages>10623-10639</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR‐140‐5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR‐140‐5p was upregulated in RCC tissues, whereas Krüppel‐like factor 9 (KLF9) was downregulated and correlated inversely with miR‐140‐5p in RCC tissues. miR‐140‐5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR‐140‐5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR‐140‐5p significantly suppressed the expression of KLF9 by binding to the 3ʹ‐UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv7.1 and KvLQT1) expression by binding to the site (−841/−827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR‐140‐5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies.</abstract><cop>United States</cop><pmid>32596959</pmid><doi>10.1096/fj.202000088RR</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions - genetics Animals Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - pathology Cell Line Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Disease Progression Down-Regulation - genetics Female Gene Expression Regulation, Neoplastic - genetics Genes, Tumor Suppressor - physiology HEK293 Cells Humans KCNQ1 KCNQ1 Potassium Channel - genetics Kidney Neoplasms - genetics Kidney Neoplasms - pathology KLF9 Kruppel-Like Transcription Factors - genetics Liver Neoplasms - genetics Liver Neoplasms - pathology Lung Neoplasms - genetics Lung Neoplasms - pathology Male Mice Mice, Inbred BALB C Mice, Nude MicroRNAs - genetics Middle Aged miR‐140‐5p proliferation/invasion/metastasis renal cell carcinoma Up-Regulation - genetics |
| title | The miR‐140‐5p/KLF9/KCNQ1 axis promotes the progression of renal cell carcinoma |
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