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

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.

• Authors: Pengli Wang, Dan Zheng, Hongyang Qi, Qi Gao
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 35 Issue 7 Pg. e22782 (Jul 2021) ISSN: 1099-0461 [Electronic] United States
• PMID: 33896068 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

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

Topics

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