MicroRNA-485 plays tumour-suppressive roles in colorectal cancer by directly targeting GAB2

Oncol Rep. 2018 Jul;40(1):554-564. doi: 10.3892/or.2018.6449. Epub 2018 May 17.

Abstract

Colorectal cancer (CRC) is reported to be the third most common cancer and the fourth leading cause of cancer-related deaths around the world. MicroRNA-485 (miR-485) has been reported to be aberrantly expressed and play important roles in several types of human malignancy. However, the expression level, biological functions and underlying molecular mechanisms of miR-485 in CRC remain unclear. Therefore, the aim of the present study was to determine miR-485 expression levels and their clinical significance in CRC and to explore the functions and underlying mechanisms of miR-485 in this disease. In the present study, miR-485 was lowly expressed in CRC tissues and cell lines. Decreased miR-485 expression was associated with tumour size, lymph node metastasis, distant metastasis and TNM stage. Functional assays indicated that upregulation of miR-485 impaired CRC cell proliferation, invasion and induced cell apoptosis. Grb2-associated binding 2 (GAB2) was identified as a direct target of miR-485 in CRC. GAB2 was upregulated in CRC tissues and was negatively correlated with the miR-485 expression level. Furthermore, GAB2 knockdown simulated the tumour-suppressing roles of miR-485 overexpression in CRC cells. Moreover, restored GAB2 expression reversed the effects of miR-485 overexpression in CRC cells. In addition, miR-485 suppressed the AKT and ERK signalling pathways in CRC by directly targeting GAB2. Collectively, these findings demonstrate that miR-485 may play tumour suppressive roles in CRC by directly targeting GAB2 and indirectly regulating AKT and ERK signalling pathways, suggesting that miR-485 may be a potential therapeutic target for patients with this disease.

Publication types

  • Retracted Publication

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Aged
  • Apoptosis / genetics
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor
  • HCT116 Cells
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • MAP Kinase Signaling System / genetics
  • Male
  • MicroRNAs / genetics*
  • Middle Aged

Substances

  • Adaptor Proteins, Signal Transducing
  • GAB2 protein, human
  • MIRN485 microRNA, human
  • MicroRNAs