Downregulation of OIP5-AS1 affects proNGF-induced pancreatic cancer metastasis by inhibiting p75NTR levels

Aging (Albany NY). 2021 Apr 3;13(7):10688-10702. doi: 10.18632/aging.202847. Epub 2021 Apr 3.

Abstract

We aimed to explore the mechanism by which long non-coding RNA (lncRNA) OIP5-AS1 affects proNGF (precursor nerve growth factor)-induced pancreatic cancer metastasis by targeting the miR-186-5p/NGFR axis. Bioinformatics was used to analyse whether OIP5-AS1 targets miR-186-5p/NGFR and their expression characteristics in pancreatic cancer. OIP5-AS1 and NGFR were overexpressed in pancreatic cancer, and their levels showed a significant positive correlation. Clinical trials also demonstrated that high expression of OIP5-AS1 and NGFR and low expression of miR-186-5p played a pro-cancer role in pancreatic cancer. MiR-186-5p inhibited the migration and invasion of colon cancer cells by targeting NGFR-regulated p75NTR. OIP5-AS1 regulated the action of miR-186-5p on NGFR mRNA and p75NTR by targeting miR-186-5p. Downregulation of NGFR inhibited the expression of p75NTR protein and blocked the role of proNGF in promoting the migration and invasion of pancreatic cancer cells. Animal experiments also showed that the knockdown of miR-186-5p promoted cancer via the expression of NGFR mRNA and p75NTR protein, while the downregulation of proNGF blocked the effects. OIP5-AS1, as a ceRNA, promotes the progression of pancreatic cancer by targeting miR-186-5p/NGFR and affecting the prognosis of patients, which may be related to the action of proNGF.

Keywords: long non-coding RNA OIP5-AS1; microRNA-186-5p; nerve growth factor receptor; pancreatic cancer; pro-nerve growth factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Cell Line, Tumor
  • Databases, Factual
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Signal Transduction / physiology

Substances

  • NGFR protein, human
  • Nerve Tissue Proteins
  • Protein Precursors
  • RNA, Long Noncoding
  • Receptors, Nerve Growth Factor
  • long noncoding RNA OIP5, human
  • pro-nerve growth factor, human
  • Nerve Growth Factor