461 MICRORNA-29 FAMILY AS TUMOR SUPPRESSIVE MICRORNAS IN RENAL CELL CARCINOMA: MICRORNA-29A INHIBITS CELL MIGRATION AND INVASION TARGETING FOCAL ADHESION AND ECM PATHWAYS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (III)1 Apr 2013461 MICRORNA-29 FAMILY AS TUMOR SUPPRESSIVE MICRORNAS IN RENAL CELL CARCINOMA: MICRORNA-29A INHIBITS CELL MIGRATION AND INVASION TARGETING FOCAL ADHESION AND ECM PATHWAYS Tomokazu Yonezawa, Hideki Enokida, Hirofumi Yoshino, Hideo Hidaka, Takeshi Yamasaki, Toshihiko Itesako, Naohiko Seki, and Masayuki Nakagawa Tomokazu YonezawaTomokazu Yonezawa Kaghosima city, Japan More articles by this author , Hideki EnokidaHideki Enokida Kaghosima city, Japan More articles by this author , Hirofumi YoshinoHirofumi Yoshino Kaghosima city, Japan More articles by this author , Hideo HidakaHideo Hidaka Kaghosima city, Japan More articles by this author , Takeshi YamasakiTakeshi Yamasaki Kaghosima city, Japan More articles by this author , Toshihiko ItesakoToshihiko Itesako Kaghosima city, Japan More articles by this author , Naohiko SekiNaohiko Seki Chiba city, Japan More articles by this author , and Masayuki NakagawaMasayuki Nakagawa Kaghosima city, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1852AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A growing body of evidence suggests that microRNAs (miRNAs) contribute to human cancer progression, development, and metastasis, including renal cell carcinoma (RCC). Our previous miRNA expression signature revealed that miR-29-family (miR-29a/b/c) was significantly reduced in clinical RCC specimens. The aim of the study was to investigate the functional significance of miR-29-family and to explore the novel molecular pathways and responsibility genes regulated by miR-29a/b/c in RCC. METHODS Gain-of-function studies were performed to investigate cancer cell proliferation, migration and invasion by mature miRNAs transfection into RCC cell lines (A498 and 786-O). To identify the biological processes or pathways potentially regulated by the miR-29-family, we applied genome-wide gene expression analysis and in silico study; TargetScan database and GENECODIS software, which assigned a number of the putative miRNA targets to known pathways in KEGG [http://www.genome.jp/kegg/pathway.html]. The expression levels of miR-29-family target genes were verified using public database of Gene Expression Omnibus (GEO) in clinical RCCs. In these microarray expression data, we examined 78 clinical RCCs and 18 normal kidney tissues. RESULTS Expression levels of miR-29-family were significantly reduced in clinical RCCs compared to adjacent non-cancerous tissues (P<0.001). Restoration of each miR-29-family significantly inhibited cancer cell proliferation, migration, and invasion in the RCC cell lines. The expression and in silico analysis showed that miR-29-family appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in ‘focal adhesion' and ‘ECM (extra-cellular matrix)-receptor interaction' signaling pathways (P<0.05). Among two pathways, 45 genes were putative targets regulated by miR-29-family (29a/b/c). Gene expression data showed that three genes (COL5A, LAMC1, and VEGFA) were significantly up-regulated in clinical RCCs compared with normal kidney tissues. CONCLUSIONS miR-29-family functioned as pivotal suppressor of cell migration and invasion in RCC through targeting ‘focal adhesion' and ‘ECM' signaling pathways. Elucidation of tumor suppressive miR-29-family-mediated cancer pathways and putative targets might be provided the novel molecular mechanisms to understand tumor progression or distant metastasis of RCC. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e189 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomokazu Yonezawa Kaghosima city, Japan More articles by this author Hideki Enokida Kaghosima city, Japan More articles by this author Hirofumi Yoshino Kaghosima city, Japan More articles by this author Hideo Hidaka Kaghosima city, Japan More articles by this author Takeshi Yamasaki Kaghosima city, Japan More articles by this author Toshihiko Itesako Kaghosima city, Japan More articles by this author Naohiko Seki Chiba city, Japan More articles by this author Masayuki Nakagawa Kaghosima city, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...