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

被引:71
|
作者
Huang, Wenhua [1 ]
Su, Xinya [1 ]
Yan, Wei [1 ]
Kong, Zhe [1 ]
Wang, Dan [1 ]
Huang, Yan [1 ]
Zhai, Qiaoli [2 ]
Zhang, Xiaowei [2 ]
Wu, Hai [1 ]
Li, Yao [1 ]
Li, Tao [2 ]
Wan, Xuechao [1 ]
机构
[1] Fudan Univ, Sch Life Sci, Shanghai 200438, Peoples R China
[2] Cent Hosp Zibo, Ctr Translat Med, Zibo 255036, Peoples R China
来源
PROSTATE | 2018年 / 78卷 / 16期
基金
中国国家自然科学基金;
关键词
androgen receptor; long non-coding RNA; prognostic marker; prostate cancer; TMPO-AS1; LONG NONCODING RNAS; ANDROGEN-RECEPTOR; THERAPEUTIC TARGETS; IDENTIFICATION; PROLIFERATION; TRANSCRIPTION; BIOMARKERS; INVASION; PROGRAM;
D O I
10.1002/pros.23700
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1248 / 1261
页数:14
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