4.5 Article

MicroRNA-126 inhibits tumor cell invasion and metastasis by downregulating ROCK1 in renal cell carcinoma

Journal

MOLECULAR MEDICINE REPORTS
Volume 13, Issue 6, Pages 5029-5036

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5160

Keywords

microRNA-126; renal cell carcinoma; Rho associated coiled-coil containing protein kinase 1; cell invasion

Funding

  1. National Natural Science Foundation of China [NSFC 81502195]
  2. Medicine and Health Science Technology Development Project of Shandong Province [2011HW028]

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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.

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