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MicroRNA-30c inhibits pancreatic cancer cell proliferation by targeting twinfilin 1 and indicates a poor prognosis

World J Gastroenterol. 2019 Nov 14;25(42):6311-6321. doi: 10.3748/wjg.v25.i42.6311.

Abstract

Background: Studies have reported that microRNA-30c (miR-30c) has vital functions in the development and progression of multiple cancers.

Aim: To investigate the clinical significance and role of miR-30c in pancreatic cancer.

Methods: MiR-30c and twinfilin 1 (TWF1) expression levels were analyzed in Gene Expression Omnibus datasets and validated in human pancreatic cancer by quantitative real-time polymerase chain reaction (RT-qPCR). The effects of miR-30c on pancreatic cancer cell growth, apoptosis, and cell cycle were evaluated by CCK-8 and flow cytometry assays. Furthermore, the in vivo effects were investigated using a subcutaneous xenograft experiment. Target gene prediction software and luciferase reporter assays were used to identify TWF1 as a direct target of miR-30c.

Results: The expression of miR-30c was significantly decreased in pancreatic cancer tissues and associated with survival. Gain- and loss-of-function assays showed that miR-30c suppressed pancreatic cancer cell proliferation in vitro and in vivo. RT-qPCR, Western blot, and luciferase reporter assays showed that miR-30c directly targeted TWF1. The expression level of miR-30c was negatively correlated with TWF1 expression in pancreatic cancer tissues. Furthermore, the effects of ectopic miR-30c were rescued by TWF1 overexpression.

Conclusion: Our results identified the role of the miR-30c/TWF1 axis in pancreatic cancer progression and demonstrated that miR-30c might serve as a prognostic biomarker and therapeutic target for pancreatic cancer.

Keywords: MicroRNA-30c; Pancreatic cancer; Proliferation; Twinfilin 1.

MeSH terms

  • Aged
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • MIRN30b microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Mirn30d microRNA, mouse
  • Ptk9 protein, mouse
  • TWF1 protein, human
  • Protein-Tyrosine Kinases