Plasmacytoma variant translocation 1 inhibits miR-515-5p function and modulates high mobility group B3 to promote the growth of prostate cancer cells

Andrology. 2023 May;11(4):641-650. doi: 10.1111/andr.13285. Epub 2022 Sep 11.

Abstract

Aim: This study is performed to analyze the role of long non-coding RNA plasmacytoma variant translocation 1 in prostate cancer.

Methods and materials: Plasmacytoma variant translocation 1, miR-515-5p, and high mobility group B3 mRNA expressions were examined using quantitative real-time polymerase chain reaction and immunohistochemistry. After gain-of-function and loss-of-function models were established, the changes in cell proliferation, migration, and invasion were evaluated using cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and Transwell experiments. Validation of the targeting relationships between plasmacytoma variant translocation 1 and miR-515-5p, and between miR-515-5p and high mobility group B3 was conducted using bioinformatics prediction, a dual-luciferase reporter assay, and an RNA immunoprecipitation experiment. Moreover, the effects of plasmacytoma variant translocation 1 and miR-515-5p on high mobility group B3 protein expression were examined using Western blot.

Results: Plasmacytoma variant translocation 1 expression and high mobility group B3 expression were up-regulated in prostate cancer tissues and cell lines while miR-515-5p expression was down-regulated. Plasmacytoma variant translocation 1 knockdown restrained the proliferation, migration, and invasion of LNCaP and DU145 cells in vitro, and the transfection with miR-515-5p inhibitors reversed these effects. Mechanistically, plasmacytoma variant translocation 1 could repress the function of miR-515; high mobility group B3 was proved to be a target gene of miR-515-5p, and its expression could be indirectly positively modulated by plasmacytoma variant translocation 1.

Conclusion: Plasmacytoma variant translocation 1 accelerates prostate cancer progression by repressing miR-515-5p's function to upregulate high mobility group B3 expression.

Keywords: HMGB3; PVT1; miR-515-5p; prostate cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Male
  • MicroRNAs* / metabolism
  • Plasmacytoma*
  • Prostatic Neoplasms* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • MIRN515 microRNA, human