MiR-30a suppresses metastasis of gastric adenocarcinoma via targeting FAPα

Cancer Biomark. 2020;27(4):471-484. doi: 10.3233/CBM-190314.

Abstract

Background: Gastric cancer is one of the leading causes of death worldwide. MicroRNA-30a (miR-30a) has been demonstrated to be involved in several types of cancer development.

Objective: We aimed to identify the molecular mechanism of miR-30a in gastric cancer.

Methods: We investigated the expression of miR-30a in gastric cancer tissues by qRT-PCR. The role of miR-30a on the metastasis and proliferation of gastric cancer was evaluated by cell migration assay, CCK-8 assay and tumor peritoneal dissemination model. The target of miR-30a in gastric cancer was identified.

Results: We discovered that miR-30a was significantly downregulated in gastric cancer tissues compared with adjacent nonmalignant tissues. The expression of miR-30a was inversely correlated with progression of gastric cancer. Gain- and loss-of function revealed that miR-30a acted as a potent tumor suppressor in gastric cancer. Re-expressed miR-30a inhibited gastric cancer cells migration, knock down miR-30a have the opposite effects. Furthermore, overexpression of miR-30a suppressed tumor peritoneal dissemination in vivo. We identified that fibroblast activation protein α (FAPα) was a direct target of miR-30a. The relative expression of FAPα was significantly higher in gastric cancer tissues compared with adjacent nonmalignant tissues. Inhibition of FAPα could recapitulate the effects of miR-30a, and overexpression of FAPα could abrogate the effect of miR-30a.

Conclusion: MiR-30a inhibited gastric cancer metastasis by targeting FAPα, suggesting that miR-30a may function as a novel tumor suppressor in gastric cancer.

Keywords: FAPα; gastric cancer; metastasis; microRNA-30a; proliferation.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Endopeptidases
  • Epithelial-Mesenchymal Transition
  • Female
  • Gelatinases / genetics
  • Gelatinases / metabolism*
  • Genes, Tumor Suppressor
  • Humans
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / pathology
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN30b microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases