title: miR-134 functions as a tumor suppressor in cell proliferation and epithelial-to-mesenchymal Transition by targeting KRAS in renal cell carcinoma cells.
abstract: Aberrant microRNAs (miRNAs) are reported to contribute to the pathogenesis of most human malignancies. The miRNA, miR-134, has been found to be downregulated in renal cell carcinoma (RCC), but its function in the disease is unknown. The aims of this study were to detect the expression of miR-134 in human RCC samples and explore its function in RCC cell lines. Real-time qualitative polymerase chain reaction (qPCR) was used to quantify miR-134 in human RCC samples. Assays for cell cycle, viability, migration, and invasion were performed to assess the phenotypic changes in RCC cells. A luciferase reporter assay was carried out to confirm whether KRAS (Kirsten rat sarcoma viral oncogene homolog) is a direct target of miR-134. Western blot was used to identify the potential signaling pathways that had an impact on RCC cell growth and alterations of markers for epithelial-mesenchymal transition (EMT), which affected metastasis by miR-134. miR-134 was found to be downregulated in RCC samples (p<0.05), while overexpression of miR-134 suppressed proliferation (p<0.05) by triggering G1/G0 cell cycle arrest (p<0.05). Forced expression of miR-134 could also inhibit migration (p<0.05) and invasion (p<0.05) by blocking EMT in RCC cell lines. KRAS was identified as a target of miR-134, and miR-134 may act as a tumor suppressor through the KRAS-related MAPK/ERK pathway other than PI3K/AKT signaling. Thus, miR-134 may function as a tumor suppressor in cell proliferation and EMT by targeting KRAS in RCC cells.
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Yiyang
authors: Y
authors: Liu
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Mingcong
authors: M
authors: Zhang
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Jian
authors: J
authors: Qian
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Meiling
authors: M
authors: Bao
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Xiaoxin
authors: X
authors: Meng
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Shaobo
authors: S
authors: Zhang
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Ruizhe
authors: R
authors: Zhao
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Shuang
authors: S
authors: Li
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Qiang
authors: Q
authors: Cao
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Pu
authors: P
authors: Li
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Xiaobing
authors: X
authors: Ju
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Qiang
authors: Q
authors: Lu
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Jie
authors: J
authors: Li
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Pengfei
authors: P
authors: Shao
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Chao
authors: C
authors: Qin
authors: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Changjun
authors: C
authors: Yin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001665:Binding Sites; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D034622:RNA Interference; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins