title: miR-148a suppresses human renal cell carcinoma malignancy by targeting AKT2.
abstract: MicroRNA-148a (miR-148a) has been reported to be deregulated in different tumor types, whereas the biological function of miR-148a in renal cell carcinoma (RCC) largely remains unexplored. In the present study we investigated the clinical significance, biological effects, and the underlying molecular mechanisms of miR-148 in RCC. Here, we showed that miR-148a was significantly downregulated in RCC tissues and cell lines. Low expression of miR-148a in RCC tissues was associated with large tumor size, advanced TNM stage, and lymph node metastasis. Functional assays revealed that overexpression of miR-148a significantly inhibited RCC cell proliferation, colony formation, migration and invasion in vitro and suppressed RCC xenograft tumor growth in vivo. In addition, using quantitative RT-PCR (qRT-PCR), western blot analysis and luciferase reporter assays, AKT2 was confirmed to be a direct target of miR-148a. AKT2 expression was upregulated, and was negatively correlated with miR-148a expression in RCC tissues (r=-0.641, P<0.001). Silencing of AKT2 phenotypically copied miR-148a-induced phenotypes, whereas re-expression of AKT2 reversed the suppressive effects of miR-148a in RCC cells. Further mechanistic investigations showed that miR-148a exerted its antitumor activity via inhibition of the AKT pathway in vitro and in vivo. Taken together, these findings suggest that miR-148a functions as tumor suppressor in RCC by targeting AKT2.
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Wenfa
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Guanyuan
authors.initials: G
authors.lastname: Nie
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Guolu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China.
authors.forename: Mingting
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt