Tumor suppressor role of miR-3622b-5p in ERBB2-positive cancer

Oncotarget. 2017 Apr 4;8(14):23008-23019. doi: 10.18632/oncotarget.14968.

Abstract

Over-expression or amplification of ERBB2 is observed in multifarious carcinomas. However, the molecular mechanism of ERBB2 downregulation in ERBB2-positive cancers remains obscure. This experiment investigated the suppressive role of miR-3622b-5p in ERBB2-positive breast and gastric cancers. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in HEK-293T, SK-BR-3 and MCF-10A cells suggested that ERBB2 was the target gene of miR-3622b-5p. Over-expressed miR-3622b-5p reduced the protein level of ERBB2, weakened the activation of mTORC1/S6, and induced the apoptosis of ERBB2-positive cancer cells. MiR-3622b-5p was significantly down-regulated in breast and gastric cancer tissues. This down-regulation in ERBB2-positive breast and gastric cancer tissues was more obvious than that in ERBB2-negative breast and gastric cancer tissues. MiR-3622b-5p turned ERBB2-positive cancer cells more vulnerable to the apoptosis induced by cisplatin and 5-fluorouracil. Taken together, miR-3622b-5p is involved in the proliferation and apoptosis of human ERBB2-positive cancer cells via targeting ERBB2/mTORC1 signaling pathway.

Keywords: ERBB2; apoptosis; cancer; miR-3622b-5p; proliferation.

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / genetics*
  • Receptor, ErbB-2 / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transfection

Substances

  • MicroRNAs
  • ERBB2 protein, human
  • Receptor, ErbB-2