Portal de Periódicos da CAPES

MicroRNA-218 Inhibits Cell Migration and Invasion in Renal Cell Carcinoma through Targeting Caveolin-2 Involved in Focal Adhesion Pathway

2013; Lippincott Williams & Wilkins; Volume: 190; Issue: 3 Linguagem: Inglês

10.1016/j.juro.2013.02.089

1527-3792

Takeshi Yamasaki, Naohiko Seki, Hirofumi Yoshino, Toshihiko Itesako, Hideo Hidaka, Yasutoshi Yamada, Shuichi Tatarano, Tomokazu Yonezawa, Takashi Kinoshita, Masayuki Nakagawa, Hideki Enokida,

Extracellular vesicles in disease

No AccessJournal of UrologyInvestigative Urology1 Sep 2013MicroRNA-218 Inhibits Cell Migration and Invasion in Renal Cell Carcinoma through Targeting Caveolin-2 Involved in Focal Adhesion Pathway Takeshi Yamasaki, Naohiko Seki, Hirofumi Yoshino, Toshihiko Itesako, Hideo Hidaka, Yasutoshi Yamada, Shuichi Tatarano, Tomokazu Yonezawa, Takashi Kinoshita, Masayuki Nakagawa, and Hideki Enokida Takeshi YamasakiTakeshi Yamasaki Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Naohiko SekiNaohiko Seki Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan , Hirofumi YoshinoHirofumi Yoshino Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Toshihiko ItesakoToshihiko Itesako Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Hideo HidakaHideo Hidaka Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Yasutoshi YamadaYasutoshi Yamada Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Shuichi TataranoShuichi Tatarano Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Tomokazu YonezawaTomokazu Yonezawa Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , Takashi KinoshitaTakashi Kinoshita Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan , Masayuki NakagawaMasayuki Nakagawa Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan , and Hideki EnokidaHideki Enokida Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.089AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Our microRNA expression signature of renal cell carcinoma revealed that miR-218 expression was significantly decreased in cancer tissues, suggesting that miR-218 is a candidate tumor suppressor. We investigated the functional significance of miR-218 in cancer cells and identified what are to our knowledge novel miR-218 mediated cancer pathways in renal cell carcinoma. Materials and Methods: Gain of function studies using mature miR-218 were performed to investigate cell proliferation, migration and invasion in the A498 and 786-O renal cell carcinoma cell lines. To identify miR-218 mediated molecular pathways and responsible genes in renal cell carcinoma, we used gene expression and in silico database analyses. Loss of function assays were performed to investigate the functional significance of miR-218 target genes. Results: Restoration of mature miR-218 significantly inhibited RCC cell proliferation, migration and invasion. Gene expression studies and luciferase reporter assays showed that CAV2 involved in the focal adhesion pathway was directly regulated by miR-218. A silencing study of CAV2 revealed significant inhibition of cell proliferation, migration and invasion. CAV2 mRNA and protein expression was significantly up-regulated in renal cell carcinoma clinical specimens. Conclusions: Loss of tumor suppressive miR-218 enhances cancer cell migration and invasion through dysregulation of the focal adhesion pathway, especially CAV2 as an oncogenic function in renal cell carcinoma. Tumor suppressive microRNA mediated cancer pathways and responsible genes provide new insights into the potential mechanisms of renal cell carcinoma oncogenesis and metastasis. References 1 : Renal cell carcinoma: focus on safety and efficacy of temsirolimus. Clin Med Insights Oncol2010; 4: 143. Google Scholar 2 : Kidney cancer working group report. Jpn J Clin Oncol2010; 40: i51. Google Scholar 3 : Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet2008; 9: 102. Google Scholar 4 : MicroRNAs and cancer: past, present, and potential future. Mol Cancer Ther2008; 7: 3655. Google Scholar 5 : Tumor suppressive microRNA-1285 regulates novel molecular targets: aberrant expression and functional significance in renal cell carcinoma. Oncotarget2012; 3: 44. Google Scholar 6 : The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer. Br J Cancer2011; 104: 808. Google Scholar 7 : Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma. Br J Cancer2011; 105: 833. Google Scholar 8 : The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer. Cancer Res2011; 71: 5765. Google Scholar 9 : MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer Res2011; 71: 2381. Google Scholar 10 : miR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet2010; 6. e1000879. Google Scholar 11 : miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer. Int J Oncol2011; 39: 13. Google Scholar 12 : TNM Classification of Malignant Tumours. International Union Against Cancer (UICC) In: . New York: Wiley-Liss2002: 255. Google Scholar 13 : Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol2011; 38: 209. Google Scholar 14 : miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma. Oncotarget2011; 2: 29. Google Scholar 15 : miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer2010; 102: 883. Google Scholar 16 : miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-β. Biochem Biophys Res Commun2010; 402: 135. Google Scholar 17 : Focal adhesion motility revealed in stationary fibroblasts. Science1999; 286: 1172. Google Scholar 18 : Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting. Cancer Res2010; 70: 10392. Google Scholar 19 Gao C, Zhang Z and Liu W: Reduced microRNA-218 expression is associated with high nuclear factor kappa B activation in gastric cancer. Cancer 116: 41. Google Scholar 20 : Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev2008; 27: 715. Google Scholar 21 : Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res2007; 13: 90. Google Scholar 22 : Interactions of EGFR and caveolin-1 in human glioblastoma cells: evidence that tyrosine phosphorylation regulates EGFR association with caveloae. Oncogene2004; 23: 6967. Google Scholar 23 : Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation. Am J Clin Pathol2003; 120: 93. Google Scholar 24 : Caveolin-1 and caveolin-2, together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis. Cancer Res2003; 63: 2864. Google Scholar 25 : Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev2009; 28: 335. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLaguna M (2020) Re: Development and Validation of a Robust Multigene Signature as an Aid to Predict Early Relapse in Stage I-III Clear Cell and Papillary Renal Cell CancerJournal of Urology, VOL. 204, NO. 4, (875-875), Online publication date: 1-Oct-2020.Atala A (2019) Re: Estrogen Receptor β Promotes Renal Cell Carcinoma Progression via Regulating LncRNA HOTAIR-miR-138/200c/204/217 Associated CeRNA NetworkJournal of Urology, VOL. 202, NO. 3, (461-461), Online publication date: 1-Sep-2019.Atala A (2016) Re: Regulation of UHRF1 by Dual-Strand Tumor-Suppressor MicroRNA-145 (miR-145-5p and miR-145-3p): Inhibition of Bladder Cancer Cell AggressivenessJournal of Urology, VOL. 196, NO. 4, (1314-1314), Online publication date: 1-Oct-2016.Atala A (2016) Re: Human Schlafen 5 (SLFN5) is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma CellsJournal of Urology, VOL. 195, NO. 4 Part 1, (1169-1169), Online publication date: 1-Apr-2016.Ishihara T, Seki N, Inoguchi S, Yoshino H, Tatarano S, Yamada Y, Itesako T, Goto Y, Nishikawa R, Nakagawa M and Enokida H (2014) Expression of the Tumor Suppressive miRNA-23b/27b Cluster is a Good Prognostic Marker in Clear Cell Renal Cell CarcinomaJournal of Urology, VOL. 192, NO. 6, (1822-1830), Online publication date: 1-Dec-2014.Andersson K (2013) This Month in Investigative UrologyJournal of Urology, VOL. 190, NO. 3, (829-830), Online publication date: 1-Sep-2013. Volume 190Issue 3September 2013Page: 1059-1068 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordskidneycarcinoma, renal cellMIRN218 microRNA, humancaveolin 2focal adhesionsAcknowledgmentsM. Miyazaki provided laboratory assistance.MetricsAuthor Information Takeshi Yamasaki Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Equal study contribution. More articles by this author Naohiko Seki Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan Equal study contribution. More articles by this author Hirofumi Yoshino Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Toshihiko Itesako Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Hideo Hidaka Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Yasutoshi Yamada Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Shuichi Tatarano Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Tomokazu Yonezawa Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Takashi Kinoshita Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan More articles by this author Masayuki Nakagawa Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Hideki Enokida Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan More articles by this author Expand All Advertisement PDF downloadLoading ...