1. MicroRNA-126 inhibits tumor cell invasion and metastasis by downregulating ROCK1 in renal cell carcinoma
- Author
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Lei Luo, Da Hai Dong, Xue‑Mei Ding, Xiao Cheng Ma, Li Jiang Sun, Bin Li, and Gui‑Ming Zhang
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Cell ,Rho associated coiled-coil containing protein kinase 1 ,Gene Expression ,urologic and male genital diseases ,Biochemistry ,Metastasis ,0302 clinical medicine ,Cell Movement ,ROCK1 ,3' Untranslated Regions ,Aged, 80 and over ,rho-Associated Kinases ,Articles ,Cell cycle ,Middle Aged ,cell invasion ,Kidney Neoplasms ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,RNA Interference ,Signal Transduction ,renal cell carcinoma ,MAP Kinase Signaling System ,Down-Regulation ,Biology ,03 medical and health sciences ,Cell Line, Tumor ,microRNA ,Genetics ,medicine ,Humans ,Neoplasm Invasiveness ,Molecular Biology ,Protein kinase B ,Carcinoma, Renal Cell ,Aged ,Cell Proliferation ,Neoplasm Staging ,Binding Sites ,Oncogene ,Cell growth ,medicine.disease ,MicroRNAs ,030104 developmental biology ,Cancer research ,microRNA-126 ,Neoplasm Grading ,Proto-Oncogene Proteins c-akt - Abstract
MicroRNAs (miRNAs) are involved in cancer development and progression. Renal cell carcinoma (RCC) frequently undergoes metastasis and has a high mortality rate. The current study measured miRNA-126 (miR-126) expres- sion levels in 128 pairs of clear cell RCC and adjacent normal kidney tissue samples by reverse transcription-quantitative polymerase chain reaction, and analyzed the association between miR-126 and various clinicopathological param- eters. In addition, cell proliferation, wound healing and cell invasion assays were conducted using RCC cells over- expressing miR-126. Potential miR-126 target genes and the signaling pathways that may be regulated by miR-126 were then examined. miR‑126 expression was significantly reduced in patients with metastatic RCC compared with patients without metastasis. Consistently, overexpression of miR‑126 in RCC cells significantly inhibited cell prolifera - tion, migration and invasion in vitro compared with negative control miRNA. A luciferase reporter assay demonstrated that miR-126 targets Rho associated coiled-coil containing protein kinase 1 (ROCK1) by directly binding the 3'-untrans- lated region. Furthermore, western blotting identified miR-126 as an important regulator of the AKT and extracel- lular signal-regulated 1/2 signaling pathways. The results of the present study indicate that miR-126 inhibits RCC cell proliferation, migration and invasion by downregulating ROCK1. These findings suggest that miR‑126 may be valu - able as a potential target for therapeutic intervention in RCC.
- Published
- 2015