title: miR-148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells.
abstract: MicroRNA (miR) can exert various biological functions by targeting oncogenes or tumor suppressor genes in numerous human malignancies. Recent evidence has shown that miR-148a increases the drug sensitivity of various cancer cells. Herein, we show that ectopic expression of miR-148a induces apoptosis, reduces clonogenicity, and increases the sensitivity to TRAIL and cisplatin in renal cancer cells. The luciferase reporter assay showed that miR-148a negatively regulated ras-related protein 14 (Rab14) expression by binding to the miR-148a binding site in the 3' untranslated region (3'UTR) of Rab14. Rab14-specific siRNA-induced downregulation of Rab14 increases the sensitivity to cisplatin, while forced expression of Rab14 lacking 3'-UTR abrogated the pro-apoptotic function of miR-148a in renal cancer cells. These findings suggest that miR-148a acts as a tumor suppressor and holds great potential for renal cancer therapy by directly targeting Rab14.
authors.affiliation: Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: Eun-Ae
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: Tae Ghab
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: Eon-Gi
authors.initials: EG
authors.lastname: Sung
authors.affiliation: Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: In-Hwan
authors.initials: IH
authors.lastname: Song
authors.affiliation: Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: Kyung-Oh
authors.initials: KO
authors.lastname: Doh
authors.affiliation: Department of Anatomy, College of Medicine, Yeungnam University, Nam-Gu, Daegu 705-717, Republic of Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C553411:Rab14 protein, human; D020691:rab GTP-Binding Proteins; D002945:Cisplatin