title: MicroRNA-148b enhances proliferation and apoptosis in human renal cancer cells via directly targeting MAP3K9.
abstract: Increasing evidence revealed that miRNAs, the vital regulators of gene expression, are involved in various cellular processes, including cell growth, differentiation, apoptosis and progression. In addition, miRNAs act as oncogenes and/or tumor suppressors. The present study aimed to verify the potential roles of miR148b in human renal cancer cells. miR‑148b was found to be downregulated in human renal cancel tissues and human renal cancer cell lines. Functional studies demonstrated that plasmid‑mediated overexpression of miR‑148b promoted cell proliferation, increased the S‑phase population of the cell cycle and enhanced apoptosis in the 786‑O and OS‑RC‑2 renal cancer cell lines, while it did not appear to affect the total number of viable cells according to a Cell Counting Kit‑8 assay. Subsequently, a luciferase reporter assay verified that miR148b directly targeted mitogen‑activated protein kinase (MAPK) kinase kinase 9 (MAP3K9), an upstream activator of MAPK kinase/c‑Jun N‑terminal kinase (JNK) signaling, suppressing the protein but not the mRNA levels. Furthermore, western blot analysis indicated that overexpression of miR148b in renal cancer cells inhibited MAPK/JNK signaling by decreasing the expression of phosphorylated (p)JNK. In addition, overexpression of MAP3K9 and pJNK was detected in clinical renal cell carcinoma specimens compared with that in their normal adjacent tissues. The present study therefore suggested that miR‑148b exerts an oncogenic function by enhancing the proliferation and apoptosis of renal cancer cells by inhibiting the MAPK/JNK pathway.
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xianggui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology and Laboratory of Signal Transduction and Molecular Targeted Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xia
authors.affiliation: College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Mao
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Tingmei
authors.initials: T
authors.lastname: Chen
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016196:S Phase / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C433243:MAP3K9 protein, human