MicroRNA-498 inhibits the proliferation, migration and invasion of gastric cancer through targeting BMI-1 and suppressing AKT pathway

Hum Cell. 2020 Apr;33(2):366-376. doi: 10.1007/s13577-019-00313-w. Epub 2020 Feb 13.

Abstract

Recently, microRNA-498 (miR-498) plays important effect in human cancers. Nonetheless, the role of miR-498 is still unclear in gastric cancer (GC). Therefore, this study was designed to investigate the function of miR-498 in GC tissues and cell lines (SGC-7901, BGC-823, MGC-803). The expressions of miR-498 and BMI-1 were examined in GC tissues via the RT-qPCR assay. The function of miR-498 was investigated through MTT and transwell assays. The relationship between miR-498 and BMI-1 was testified by dual luciferase assay. The protein expression of EMT markers, AKT pathway markers and BMI-1 was measured through western blot. The expression of miR-498 was decreased in GC tissues which predicted poor prognosis of GC patients. Moreover, functional analyses show that the overexpression of miR-498 inhibited the progression of GC. Furthermore, BMI-1 was a direct target of miR-498 which was upregulated in GC. Especially, the upregulation of BMI-1 recovered the suppressive effect of miR-498 in GC. In addition, miR-498 inhibited the metastasis and proliferation of GC cells through blocking EMT and AKT pathway. MiR-498, by targeting BMI-1, presents a plethora of tumor suppressor activities in GC cells.

Keywords: AKT pathway; BMI-1; Gastric cancer; MiR-498.

MeSH terms

  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Humans
  • Mitogen-Activated Protein Kinase 7*
  • Neoplasm Invasiveness / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*

Substances

  • Proto-Oncogene Proteins c-akt
  • MAPK7 protein, human
  • Mitogen-Activated Protein Kinase 7