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A novel lncRNA PLK4 up-regulated by talazoparib represses hepatocellular carcinoma progression by promoting YAP-mediated cell senescence.


ABSTRACT: A growing number of studies recognize that long non-coding RNAs (lncRNAs) are essential to mediate multiple tumorigenic processes, including hepatic tumorigenesis. However, the pathological mechanism of lncRNA-regulated liver cancer cell growth remains poorly understood. In this study, we identified a novel function lncRNA, named polo-like kinase 4 associated lncRNA (lncRNA PLK4, GenBank Accession No. RP11-50D9.3), whose expression was dramatically down-regulated in hepatocellular carcinoma (HCC) tissues and cells. Interestingly, talazoparib, a novel and highly potent poly-ADP-ribose polymerase 1/2 (PARP1/2) inhibitor, could increase lncRNA PLK4 expression in HepG2 cells. Importantly, we showed that talazoparib-induced lncRNA PLK4 could function as a tumour suppressor gene by Yes-associated protein (YAP) inactivation and induction of cellular senescence to inhibit liver cancer cell viability and growth. In summary, our findings reveal the molecular mechanism of talazoparib-induced anti-tumor effect, and suggest a potential clinical use of talazoparib-targeted lncRNA PLK4/YAP-dependent cellular senescence for the treatment of HCC.

SUBMITTER: Jia Y 

PROVIDER: S-EPMC7205816 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A novel lncRNA PLK4 up-regulated by talazoparib represses hepatocellular carcinoma progression by promoting YAP-mediated cell senescence.

Jia Yan Y   Jin Huanhuan H   Gao Liyuan L   Yang Xiang X   Wang Feixia F   Ding Hai H   Chen Anping A   Tan Shanzhong S   Zhang Feng F   Shao Jiangjuan J   Wang Shijun S   Zheng Shizhong S  

Journal of cellular and molecular medicine 20200403 9


A growing number of studies recognize that long non-coding RNAs (lncRNAs) are essential to mediate multiple tumorigenic processes, including hepatic tumorigenesis. However, the pathological mechanism of lncRNA-regulated liver cancer cell growth remains poorly understood. In this study, we identified a novel function lncRNA, named polo-like kinase 4 associated lncRNA (lncRNA PLK4, GenBank Accession No. RP11-50D9.3), whose expression was dramatically down-regulated in hepatocellular carcinoma (HCC  ...[more]

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