Impact of Oncogenic Targets Controlled by Tumor-Suppressive miR-30a-5p in Pancreatic Ductal Adenocarcinoma

Anticancer Res. 2021 Oct;41(10):4821-4836. doi: 10.21873/anticanres.15297.

Abstract

Background/aim: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease.

Materials and methods: In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples.

Results: A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells.

Conclusion: The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.

Keywords: RRM2; miR-30a-5p; microRNA; pancreatic ductal adenocarcinoma; tumor-suppressor.

MeSH terms

  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Core Binding Factor beta Subunit / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Membrane Proteins / genetics
  • MicroRNAs / genetics
  • MicroRNAs / physiology
  • Neoplasm Proteins / genetics
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Ribonucleoside Diphosphate Reductase / genetics
  • Ribonucleoside Diphosphate Reductase / metabolism
  • Survival Analysis

Substances

  • AHNAK protein, human
  • CBFB protein, human
  • Core Binding Factor beta Subunit
  • DCBLD1 protein, human
  • MIRN30a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase