Exosomal miR-182 regulates the effect of RECK on gallbladder cancer

World J Gastroenterol. 2020 Mar 7;26(9):933-946. doi: 10.3748/wjg.v26.i9.933.

Abstract

Background: As the most common biliary malignancy, gallbladder cancer (GC) is an elderly-biased disease. Although extensive studies have elucidated the molecular mechanism of microRNA 182 (miR-182) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) in various cancers, the specific role of exosomal miR-182 and RECK in GC remains poorly understood.

Aim: To explore the relationship between exosomal miR-182/RECK and metastasis of GC.

Methods: Paired GC and adjacent normal tissues were collected from 78 patients. Quantitative polymerase chain reaction was employed to detect miR-182 and exosomal miR-182 expression, and Western blotting was conducted to determine RECK expression. In addition, the effects of exosomal miR-182/RECK on the biological function of human GC cells were observed. Moreover, the double luciferase reporter gene assay was applied to validate the targeting relationship between miR-182 and RECK.

Results: Compared with normal gallbladder epithelial cells, miR-182 was highly expressed in GC cells, while RECK had low expression. Exosomal miR-182 could be absorbed and transferred by cells. Exosomal miR-182 inhibited RECK expression and promoted the migration and invasion of GC cells.

Conclusion: Exosomal miR-182 can significantly promote the migration and invasion of GC cells by inhibiting RECK; thus miR-182 can be used as a therapeutic target for GC.

Keywords: Exosome; Gallbladder cancer; Quantitative polymerase chain reaction; RECK; Therapeutic target; miR-182.

MeSH terms

  • Aged
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial Cells / drug effects
  • Exosomes / metabolism*
  • Female
  • GPI-Linked Proteins / metabolism*
  • Gallbladder / drug effects
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis

Substances

  • GPI-Linked Proteins
  • MicroRNAs
  • Mirn182 microRNA, human
  • RECK protein, human