MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction

Mol Med Rep. 2016 Jan;13(1):273-80. doi: 10.3892/mmr.2015.4557. Epub 2015 Nov 12.

Abstract

Colorectal cancer (CRC) is the third most common cancer type and the fourth leading cause of cancer‑associated mortality worldwide. MicroRNA (miR)‑1246 is involved in differentiation, invasion, metastasis and chemoresistance of certain types of tumor cells. CCNG2 encodes an unconventional cyclin homolog, cyclin G2 (CycG2), associated with growth inhibition, which correlated significantly with lymph node metastasis, clinical stage, histological grade and poor overall survival in numerous cancer types. To investigate the regulation of miR‑1246 on CycG2 expression, and their effects on proliferation and metastasis of CRC, HCT‑116 and LOVO cells were transfected with pre‑miR‑1246 anti‑miR‑1246 and their negative controls. It was demonstrated that the expression of miR‑1246 was significantly increased in CRC tissues and cell lines, which was the opposite of CycG2. miR‑1246 negatively regulated the expression of CycG2 in HCT‑116 and LOVO CRC cells. CCNG2 is a direct target of miR‑1246 in CRC cells. Overexpression of miR‑1246 induced cell proliferation, migration and invasion, while knockdown of miR‑1246 inhibited proliferation, migration and invasion in the CRC cells. Upregulation of miR‑1246 mediated the malignant progression of CRC and is partly attributed to the downregulation of the expression of CycG2. Consequently, these findings provided a molecular basis for the role of miR‑1246/CCNG2 in the progression of human CRC and suggested a novel target for the treatment of CRC.

MeSH terms

  • Aged
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Cyclin G2 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CCNG2 protein, human
  • Cyclin G2
  • MIRN1246 microRNA, human
  • MicroRNAs
  • RNA, Messenger