miR-148a suppresses human renal cell carcinoma malignancy by targeting AKT2
Authors: Zhiming Liu
Guolu Wang
Mingting Zhu
Huiyan Cao
Rong Wang
Yong Yu
Guanyuan Nie
Wenfa Yi
Xiaodong Zhang
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-148a; renal cell carcinoma; tumor suppressor; AKT2; proliferation
Affiliations: Department of Urological Surgery, People's Hospital of Qinghai, Xining, Qinghai 810007, P.R. China., Department of Medical Oncology, The Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, P.R. China.

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&lt;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. 

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PubPeer comments:
 Fig 2C.  colony formation ... determined in 786-O cells after transfection with miR-148a mimic or miR-NC . ![file] Fig 2C from [Li et al (2017)] .  Cell colony formation of A549 cells transfected with miR-592 mimic or miR-Ctrl was analyzed . ![file] These seem to be the same plates, with some colonies added or removed. , 
 Fig 7.  miR-148a inhibits the Akt pathway in vitro and in vivo. AKT2, AKT, p-AKT, mTOR and p-mTOR protein expression levels were detected in the 786-O cells transfected with miR-148a or miR-NC, and in tumor tissues from 7786-O miR-148a and 7786-O miR-NC xenograft mice. ![file] Previous appearances of the AKT band (blue box) include *[above]* Fig 5D from [Liu et al (2016)] .  The ADAM10 protein expression was measured in four HCC cell lines (SMMC-7721, Hep3B, HepG2, Huh-7) and normal hepatic cell line HL-7702 by western blot . *[below]* Fig 4D of [Dong et al (2016)] . ![file] Fig 3C from [Liu et al (2015)] . ![] Previous appearances of the loading control (green box) include Fig 3E from Liu et al (2016); and *[right]* Fig 6B from Liu et al (2015). ![] Other bands are left as an exercise for the reader. , 
 #1 UPDATE: Another sighting of the left-hand plate, though flipped through 180 deg. Fig 5D of [Lin et al (2017)] .  Cell ... colony formation ... were determined in [cotransfected SKOV3] cells. ![] , 
 - *[above]* Fig 2E.  Cell ... invasion were determined in 786-O cells after transfection with miR-148a mimic or miR-NC . - *[below]* Fig 2E F from  miR-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of FGF2 ([Xu et al 2015] . ![file] ,