miR-324-5p inhibits gallbladder carcinoma cell metastatic behaviours by downregulation of transforming growth factor beta 2 expression

Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):315-324. doi: 10.1080/21691401.2019.1703724.

Abstract

Increasing studies have demonstrated that microRNAs (miRNAs) are associated with the metastasis of gallbladder carcinoma (GBC). Recently, miR-324-5p has been reported to be a tumour-suppressive miRNA in many types of malignant cancer. However, the biological function and molecular mechanism of miR-324-5p in GBC still remain largely unknown. Here, we found that miR-324-5p expression was notably down-regulated in both GBC tissues and cells compared with that in normal controls. Downregulated miR-324-5p expression was negatively associated with the status of local invasion and lymph node metastasis and predicted a poor prognosis in GBC patients. Further functional assays revealed that restoration of miR-324-5p significantly suppressed GBC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and impeded the metastasis of GBC cells in vivo. Moreover, RNA immunoprecipitation (RIP) and dual-luciferase reporter assay confirmed that the transforming growth factor beta 2 (TGFB2) was a direct target gene of miR-324-5p in GBC cells. Mechanically, small interfering RNA (siRNA)-mediated knockdown of TGFB2 partially phenocopied the inhibitory effects of miR-324-5p overexpression on GBC cell metastatic phenotypes. In summary, our findings demonstrated that miR-324-5p targets TGFB2 expression to inhibit GBC cell metastatic behaviors, and implying miR-324-5p as a potential biomarker for diagnostic and therapeutic strategies in GBC.

Keywords: GBC; TGFB2; behaviours; metastasis; miR-324-5p.

Publication types

  • Video-Audio Media

MeSH terms

  • Cell Line, Tumor
  • Down-Regulation*
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / metabolism*
  • Gallbladder Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Transforming Growth Factor beta2 / biosynthesis*
  • Transforming Growth Factor beta2 / genetics

Substances

  • MIRN324 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • TGFB2 protein, human
  • Transforming Growth Factor beta2