Overexpression of AR-regulated lncRNA TMPO-AS1 correlates with tumor progression and poor prognosis in prostate cancer

Prostate. 2018 Dec;78(16):1248-1261. doi: 10.1002/pros.23700. Epub 2018 Aug 13.

Abstract

Background: Prostate cancer (PCa) is a leading cause of death in males all over the world; besides, the diagnosis and therapy of it are still challenging. Researchers have revealed that long non-coding RNAs (lncRNAs) play important roles in the genesis and progression of human cancers, including PCa.

Methods: Bioinformatics analysis and Kaplan-Meier survival analysis were utilized to confirm TMPO-AS1 as a diagnostic and prognostic marker. The TMPO-AS1 levels in both patient tissues and PCa cell lines were determined by qRT-PCR analysis. Moreover, the chromatin immunoprecipitation (ChIP) assay identified that TMPO-AS1 was a direct target of AR. The effect of overexpression or knockdown of TMPO-AS1 on cell proliferation, migration, cell cycle, and cell apoptosis was assessed by using CCK-8, transwell assays, and flow cytometric analysis, respectively.

Results: Based on primary screening, we found that TMPO-AS1 could be a useful diagnostic and prognostic marker for PCa, whose expression was upregulated in PCa samples and associated with poorer prognosis. Bioinformatics predictions revealed TMPO-AS1 was associated with a series of biological processes involved in PCa progression. In PCa cells, TMPO-AS1 was predominantly localized in the cytoplasm and directly down-regulated by AR. Gain/loss-of-function assays showed TMPO-AS1 overexpression increased cell proliferation by promoting cell cycle progression and promoted migration, but reduced apoptosis of PCa cells. In addition, TMPO-AS1 may be a diagnostic and prognostic marker in multiple cancer types.

Conclusions: AR-regulated lncRNA TMPO-AS1 functioned as an oncogenic lncRNA in PCa, and may be a potential diagnostic and prognostic biomarker to be used as a therapeutic target for PCa.

Keywords: TMPO-AS1; androgen receptor; long non-coding RNA; prognostic marker; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA, Long Noncoding / genetics*

Substances

  • RNA, Long Noncoding