PAX5-induced upregulation of LINC01194 exerts oncogenic properties by regulating GOLPH3 expression via miR-486-5p in prostate cancer

Eur Rev Med Pharmacol Sci. 2021 Mar;25(6):2528-2541. doi: 10.26355/eurrev_202103_25416.

Abstract

Objective: Several studies have demonstrated that long non-coding RNA can act as crucial roles during the progression of various tumors, including prostate cancer (PCa). We aimed to determine lncRNA LINC01194(LINC01194) expression in prostate cancer (PCa) and examine its influence on tumor behaviors of PCa cells.

Patients and methods: RT-PCR was performed to examine LINC01194 and PAX5's expression levels in PCa tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether PAX5 could activate the transcription of LINC01194. Cell viability, migration and invasion were assessed by CCK-8, colony formation, transwell assay and Wound-healing assays. Bioinformatics and Dual-Luciferase assays were used to investigate the interaction between LINC01194 and miR-486-5p, as well as between miR-486-5p and GOLPH3. Western blot was applied for detecting the expressions of the related proteins.

Results: LINC01194 was highly expressed in PCa specimens and cell lines. PAX5 could bind directly to LINC01194 promoter region and activate its transcription. Functionally, the proliferation and metastasis of PCa cells were substantially impeded by LINC01194 silencing in vitro and in vivo. Mechanistically, LINC01194 promoted PCa progression by serving as a sponge of miR-486-5p to increase GOLPH3 expression.

Conclusions: Our study identifies LINC01194 as a tumor promotor in PCa and implicates the LINC01194/miR-486-5p/GOLPH3 axis in the PCa progression.

MeSH terms

  • Aged
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Computational Biology
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • PAX5 Transcription Factor / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation*

Substances

  • GOLPH3 protein, human
  • MIRN486 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • RNA, Long Noncoding