MicroRNA-561-5p Inhibits Cell Proliferation and Invasion by Targeting RAC1 in Pancreatic Ductal Adenocarcinoma

Ann Clin Lab Sci. 2022 Mar;52(2):213-221.

Abstract

Objective: This study aims to investigate how miR-561-5p regulated the expression of RAC1 and whether its effects on RAC1 was associated with the proliferation, migration, invasion, and apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells.

Materials and methods: RT-qPCR was performed to assess miR-561-5p expression in human PDAC tissues. A series of in vitro experiments including cell counting Kit-8, colony formation, cell migration and invasion, and apoptosis assays were used to assess the PDAC cell biological behaviors. TargetScan v7.2 was used to identify the miR-561-5p target genes, dual-luciferase reporter assay was performed to confirm the targeted relationship between miR-561-5p and Rac family small GTPase 1 (RAC1). Also, RAC1 was upregulated in miR561-5p overexpressed PDAC cells to evaluate the functional involvement of RAC1 in miR-561-5p mediated PDAC cell proliferation and invasion.

Results: The results demonstrated that miR-561-5p expression was lower in PDAC tissues compared with in normal tissues. Overexpression of miR-561-5p inhibited PDAC cell proliferation, migration, and invasion, and promoted apoptosis in vitro, while miR-561-5p-knockdown had the opposite effects in the PDAC cell line BxPC3. Using bioinformatics analysis and dual-luciferase reporter assays, the present study revealed that RAC1 was a direct target of miR-561-5p and that RAC1 overexpression could partly rescue the suppressive effects of miR-561-5p mimics on PDAC cells.

Conclusion: The overexpression of miR-561-5p may suppress carcinogenesis in PDAC cells by targeting RAC1 and inhibit PDAC cell proliferation and invasion.

Keywords: Pancreatic ductal adenocarcinoma; Rac family small GTPase 1; cell invasion; cell proliferation; microRNA-561-5p.

MeSH terms

  • Adenocarcinoma* / pathology
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / pathology
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism

Substances

  • MIRN561 microRNA, human
  • MicroRNAs
  • RAC1 protein, human
  • rac1 GTP-Binding Protein