Silencing of TP73-AS1 impairs prostate cancer cell proliferation and induces apoptosis via regulation of TP73

Mol Biol Rep. 2022 Jul;49(7):6859-6869. doi: 10.1007/s11033-022-07141-6. Epub 2022 Feb 9.

Abstract

Background: Prostate cancer is a malignant disease that severely affects the health and comfort of the male population. The long non-coding RNA TP73-AS1 has been shown to be involved in the malignant transformation of various human cancers. However, whether TP73-AS1 contributes to prostate cancer progression has not been reported yet. Accordingly, here we aimed to report the role of TP73-AS1 in the development and progression of prostate cancer and determine its relationship with TP73.

Methods and results: TP73-AS1-specific siRNA oligo duplexes were used to silence TP73-AS1 in DU-145 and PC-3 cells. Results indicated that TP73-AS1 was upregulated whereas TP73 was downregulated in prostate cancer cells compared to normal prostate cells and there was a negative correlation between them. Besides, loss of function experiments of TP73-AS1 in prostate cancer cells strongly induced cellular apoptosis, interfered with the cell cycle progression, and modulated related pro- and anti-apoptotic gene expression. Colony formation and migration capacities of TP73-AS1-silenced prostate cancer cells were also found to be dramatically reduced.

Conclusions: Our findings provide novel evidence that suggests a chief regulatory role for the TP73-TP73-AS1 axis in prostate cancer development and progression, suggesting that the TP73/TP73-AS1 axis can be a promising diagnostic and therapeutic target for prostate cancer.

Keywords: LncRNA; Prostate cancer; TP73; TP73-AS1.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Prostatic Neoplasms* / genetics
  • RNA, Long Noncoding* / genetics
  • Tumor Protein p73 / metabolism*

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • TP73 protein, human
  • Tumor Protein p73