title: miRNA-133b and miRNA-135a induce apoptosis via the JAK2/STAT3 signaling pathway in human renal carcinoma cells.
abstract: Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In clear cell renal cell carcinoma (ccRCCs) expression of miR-133b and miR-135a is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-133b and miR-135a expression profiles in different RCC subtypes and the functional role of these miRNAs. Viability and apoptosis were examined in three different ccRCC cell lines (786-O, A498 and SN12-PM6) after over-expression of these miRNAs. The modulation of JAK2 and the JAK2/STAT3 pathways was determined by Western blot. Transient transfection of miR-133b and miR-135a reduced viability and induced apoptosis by inhibition of JAK2 expression and its phosphorylation and activation of caspase 3 and 7 in all three ccRCC cell lines. p-STAT3 and Bcl-2 expression was reduced after miRNA transfection whereas only slight influence on Bcl-2 L11 (BIM) was detected. Our results demonstrate that miR-133b and miR-135a which are down-regulated in wildtype and mutated ccRCCs, induce apoptosis in vitro by a signaling cascade involving JAK2, STAT3 and Bcl-2. Therefore, over-expression of these miRNAs seems to functionally counteract oncogenic signalling pathways in ccRCCs.
authors.affiliation: Department of Surgery, Hospital of Weifang Medical University, Weifang 261053, PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, Weifang Fifth People's Hospital, Weifang 261061, PR China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Urology, Affiliated Hospital of Weifang Medical University, Weifang 261031, PR China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Urology, Affiliated Hospital of Qingdao University, Qingdao 266003, PR China. Electronic address: sunljiangqd@sina.com.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D053614:Janus Kinase 2 / Q000096:biosynthesis* / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: C548234:MIRN133 microRNA, human; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Apoptosis; JAK2; STAT3; ccRCCs; miR-133b; miR-135a