Thioredoxin-interacting protein is a favored target of miR-125b, promoting metastasis and progression of pancreatic cancer via the HIF1α pathway

J Biochem Mol Toxicol. 2021 Jul;35(7):e22782. doi: 10.1002/jbt.22782. Epub 2021 Apr 25.

Abstract

MicroRNAs (miRs) are vital in the development of pancreatic cancer (PC) targeting several cellular processes. This study was aimed at evaluating the function of miR-125b and the mechanism involved in PC. Cell migration, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and Bromodeoxyuridine/5-bromo-2'-deoxyuridine (BrdU) study was done to establish the migration capability, cell viability, and cell proliferation, respectively. Binding sites for miR-125b were recognized by luciferase assay, and the expression of protein by Western blot and immunofluorescence assay. In vivo study was done by BALB/c nude xenograft mice for evaluating the function of miR-125b. The study showed that expression of miR-125b was elevated in PC cells and tissues and was correlated to proliferation and migration of cells. Also, overexpression of miR-125b encouraged migration, metastasis, and proliferation of BxPC-3 cells, and suppression reversed it. We also noticed that thioredoxin-interacting protein (TXNIP) was the potential target of miR-125b. The outcomes also suggested that miR-125b governed the expression of TXNIP inversely via directly attaching to the three prime untranslated region (3'-UTR) activating hypoxia-inducible factor 1α (HIF1α). Looking into the relation between HIF1α and TXNIP, we discovered that TXNIP caused the degradation and export of HIF1α by making a complex with it. The miR-125b-TXNIP-HIF1α pathway may serve as a useful strategy for diagnosing and treating PC.

Keywords: TXNIP; miR-125b: HIF1α; pancreatic cancer.

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Signal Transduction*

Substances

  • Carrier Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN125 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • TXNIP protein, human