MicroRNA‑181a promotes cell proliferation and inhibits apoptosis in gastric cancer by targeting RASSF1A

Oncol Rep. 2018 Oct;40(4):1959-1970. doi: 10.3892/or.2018.6632. Epub 2018 Aug 7.

Abstract

MicroRNA (miR)‑181a is a member of the miR‑181 family that serves a key role in the pathogenesis of various cancer types. The present study aimed to investigate the interaction between miR‑181a and Ras association domain family protein1 isoform A (RASSF1A), and their roles in gastric carcinogenesis. The interaction between miR‑181a and RASSF1A was assessed in cell lines and cancer tissues. The direct binding of miR‑181a and RASSF1A was identified using a luciferase reporting gene system. The effects of miR‑181a and RASSF1A on gastric cancer cell growth, cell cycle and apoptosis were assessed with a Cell Counting Kit‑8 assay and flow cytometry. The effects of miR‑181a on cell division cycle 25A (CDC25A), cyclin A2, cyclin D1, p21, Bcl‑2‑associated X protein (Bax) and B‑cell lymphoma‑2 (Bcl‑2) protein levels were assessed in gastric cancer cell lines. miR‑181a directly interacted with the 3'‑untranslated region of RASSF1A and downregulated RASSF1A protein expression. In tissues from patients with gastric cancer, the miR‑181a level was significantly higher in the tumor tissues and was negatively correlated with the RASSF1A protein level. RASSF1A suppressed gastric cancer cell proliferation and G1/S transition, and promoted apoptosis; whereas miR‑181a promoted cancer cell proliferation and G1/S transition, and suppressed apoptosis. RASSF1A knockdown attenuated the effects of miR‑181a downregulation on cell proliferation and apoptosis. Furthermore, miR‑181a upregulated CDC25A, cyclin A2 and Bcl‑2, and downregulated Bax protein expression in gastric cancer cell lines. These data indicate that miR‑181a promotes gastric carcinogenesis, possibly through a direct interaction with RASSF1A.

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / secondary*
  • Adult
  • Aged
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Cycle
  • Cell Proliferation*
  • Cyclin A2 / genetics
  • Cyclin A2 / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / secondary*
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • CCNA2 protein, human
  • Cyclin A2
  • MIrn181 microRNA, human
  • MicroRNAs
  • RASSF1 protein, human
  • Tumor Suppressor Proteins