miR-206 inhibits renal cell cancer growth by targeting GAK

J Huazhong Univ Sci Technolog Med Sci. 2016 Dec;36(6):852-858. doi: 10.1007/s11596-016-1674-8. Epub 2016 Dec 7.

Abstract

Renal cell cancer (RCC) remains one of the most lethal types of cancer in adults. MicroRNAs (miRNAs) play key roles in the pathogenesis of RCC. The role of miR-206 in RCC has not been fully understood. The purpose of this study was to examine the role of miR-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism. miR-206 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RCC cell lines (786-O and OS-RC-2 cells) and clinical samples. MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] method, colony formation and transwell assay were used to detect the tumor-suppressing ability of miR-206 in RCC. Luciferase assay was performed to verify the precise target of miR-206. The results showed that the expression of miR-206 was significantly down-regulated in RCC tissues and cells. The expression level of cyclin G-associated kinase (GAK), a master regulator of tumor proliferation and metastasis, was up-regulated with the decrease in miR-206 in RCC tissues as well as RCC cell lines. In addition, the miR-206 inhibitor promoted the proliferation, migration and invasion of 786-O and OS-RC-2 cells. Bioinformatics combined with luciferase and Western blot assays revealed that miR-206 inhibited the expression of GAK. Moreover, miR-206 regulates RCC cell growth partly through targeting GAK. Our study indicated that miR-206 functions as a tumor suppressor in regulating the proliferation, migration and invasion of RCC by directly targeting GAK, and it holds promises as a potential therapeutic target for RCC.

Keywords: G-associated kinase; miR-206; renal cell cancer.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN206 microRNA, human
  • MicroRNAs
  • GAK protein, human
  • Protein Serine-Threonine Kinases