NF90调节肝癌中PARP1 mRNA的稳定性。
NF90 regulates PARP1 mRNA stability in hepatocellular carcinoma.
作者信息
Song Dan, Huang Huixing, Wang Juanjuan, Zhao Yahui, Hu Xiaoding, He Funan, Yu Long, Wu Jiaxue
机构信息
Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, PR China.
Zhongshan Hospital and School of Life Science, Fudan University, Shanghai, PR China.
出版信息
Biochem Biophys Res Commun. 2017 Jun 17;488(1):211-217. doi: 10.1016/j.bbrc.2017.05.037. Epub 2017 May 6.
Poly (ADP-ribose) polymerase 1 (PARP1) is an ADP- ribosylation enzyme and plays important roles in a variety of cellular processes, including DNA damage response and tumor development. However, the post-transcriptional regulation of PARP1 remains largely unknown. In this study, we identified that the mRNA of PARP1 is associated with nuclear factor 90 (NF90) by RNA immunoprecipitation plus sequencing (RIP-seq) assay. The mRNA and protein levels of PARP1 are dramatically decreased in NF90-depleted cells, and NF90 stabilizes PARP1's mRNA through its 3'UTR. Moreover, the expression levels of PARP1 and NF90 are positively correlated in hepatocellular carcinoma (HCC). Finally, we demonstrated that NF90-depleted cells are sensitive to PARP inhibitor Olaparib (AZD2281) and DNA damage agents. Taken together, these results suggest that NF90 regulates PARP1 mRNA stability in hepatocellular carcinoma cells, and NF90 is a potential target to inhibit PARP1 activity.
聚（ADP - 核糖）聚合酶1（PARP1）是一种ADP - 核糖基化酶，在包括DNA损伤反应和肿瘤发展在内的多种细胞过程中发挥重要作用。然而，PARP1的转录后调控在很大程度上仍不清楚。在本研究中，我们通过RNA免疫沉淀测序（RIP - seq）分析确定PARP1的mRNA与核因子90（NF90）相关。在NF90缺失的细胞中，PARP1的mRNA和蛋白水平显著降低，并且NF90通过其3'非翻译区（3'UTR）稳定PARP1的mRNA。此外，在肝细胞癌（HCC）中，PARP1和NF90的表达水平呈正相关。最后，我们证明NF90缺失的细胞对PARP抑制剂奥拉帕尼（AZD2281）和DNA损伤剂敏感。综上所述，这些结果表明NF90调节肝癌细胞中PARP1 mRNA的稳定性，并且NF90是抑制PARP1活性的潜在靶点。
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