MicroRNA-126 inhibits tumor cell invasion and metastasis by downregulating ROCK1 in renal cell carcinoma.
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) expression 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 parameters. In addition, cell proliferation, wound healing and cell invasion assays were conducted using RCC cells overexpressing 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 proliferation, 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'‑untranslated region. Furthermore, western blotting identified miR‑126 as an important regulator of the AKT and extracellular 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 valuable as a potential target for therapeutic intervention in RCC.
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Gui-Ming
GM
Zhang
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Lei
L
Luo
Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Xue-Mei
XM
Ding
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Da-Hai
DH
Dong
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Bin
B
Li
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Xiao-Cheng
XC
Ma
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Li-Jiang
LJ
Sun
D020413:3' Untranslated Regions; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000235:genetics*
D020413:3' Untranslated Regions; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases