Tumor promoter role of miR‑647 in gastric cancer via repression of TP73

Mol Med Rep. 2018 Oct;18(4):3744-3750. doi: 10.3892/mmr.2018.9358. Epub 2018 Aug 6.

Abstract

It has previously been demonstrated that miRNA (miR)‑647 exhibits an important role in various cancers, and is aberrantly expressed in gastric cancer (GC). However, the exact role of miR‑647 in GC still remains unclear. The present study aimed to investigate the functional significance of miR‑647 and its target gene in GC. TargetScan and Miranda databases were used to predict the putative targets, and the prediction was validated by Dual‑luciferase Reporter Assays. To investigate whether miR‑647 affects GC cell behavior, a stable miR‑647‑overexpression/low‑expression cell line was generated by transfection with miR‑647 mimic/inhibitor. MTT, Flow Cytometry and Transwell invasion assays were performed to investigate the proliferation, cell apoptosis, migration and invasion properties of MGC‑803 cells. Additionally, reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to detect the mRNA and protein expression levels of the apoptosis‑associated genes. The results suggested that tumor protein P73 (TP73) is a target gene of miR‑647. TP73 was markedly decreased following miR‑647 overexpression and significantly increased following miR‑647 inhibition. Following overexpression of miR‑647, the proliferation, migration and invasion of MGC‑803 cells were significantly increased, whereas the percentage of apoptotic cells decreased. Conversely, the proliferation, migration and invasion of MGC‑803 cells were significantly declined, and the percentage of apoptotic cells increased following miR‑647 inhibition. In addition, the B cell lymphoma (Bcl)‑2 Associated X, Apoptosis Regulator/Bcl‑2 ratio was markedly decreased when miR‑647 was overexpressed by miRNA mimics, and significantly increased when miR‑647 expression was inhibited via an miRNA inhibitor. Overall, miR‑647 functions as a tumor promoter in GC by repressing TP73.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Protein p73 / genetics*

Substances

  • MIRN647 microRNA, human
  • MicroRNAs
  • TP73 protein, human
  • Tumor Protein p73