4.4 Article

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

Journal

PROSTATE
Volume 78, Issue 16, Pages 1248-1261

Publisher

WILEY
DOI: 10.1002/pros.23700

Keywords

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

Funding

  1. National Natural Science Foundation of China [31571330, 81773024]
  2. Open Research Funds of the State Key Laboratory of Genetic Engineering, Fudan University [SKLGE-1608]

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Background Methods 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. 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 Conclusions 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. 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.

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