Pyridoxine 5'-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

Aging (Albany NY). 2019 Apr 14;11(7):2151-2176. doi: 10.18632/aging.101908.

Abstract

Pyridoxine 5'-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.

Keywords: MALAT1; PNPO; breast cancer; miR-216b; vitamin B6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Binding, Competitive
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / enzymology*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Pyridoxaminephosphate Oxidase / antagonists & inhibitors
  • Pyridoxaminephosphate Oxidase / genetics
  • Pyridoxaminephosphate Oxidase / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Tumor Stem Cell Assay

Substances

  • MALAT1 long non-coding RNA, human
  • MIRN216 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • Receptors, Progesterone
  • Pyridoxaminephosphate Oxidase