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剪接调控因子 hnRNPU 是肝癌中 c-Myc 的一个新型转录靶标。

The splicing regulatory factor hnRNPU is a novel transcriptional target of c-Myc in hepatocellular carcinoma.

机构信息

Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, China.

South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, China.

出版信息

FEBS Lett. 2021 Jan;595(1):68-84. doi: 10.1002/1873-3468.13943. Epub 2020 Nov 7.

Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer with high mortality. Here, we found that hnRNPU is overexpressed in HCC tissues and is correlated with the poor prognosis of HCC patients. Besides, hnRNPU is of high significance in regulating the proliferation, apoptosis, self-renewal, and tumorigenic potential of HCC cells. Mechanismly, c-Myc regulates hnRNPU expression at the transcriptional level, and meanwhile, hnRNPU stabilizes the mRNA of c-MYC. We found that the hnRNPU and c-Myc regulatory loop exerts a synergistic effect on the proliferation and self-renewal of HCC, and promotes the HCC progression. Taken together, hnRNPU functions as a novel transcriptional target of c-Myc and promotes HCC progression, which may become a promising target for the treatment of c-Myc-driven HCC.

摘要

肝细胞癌(HCC)是最常见的肝癌,死亡率很高。在这里,我们发现 hnRNPU 在 HCC 组织中过表达,并与 HCC 患者的预后不良相关。此外,hnRNPU 在调节 HCC 细胞的增殖、凋亡、自我更新和致瘤潜能方面具有重要意义。在机制上,c-Myc 在转录水平上调节 hnRNPU 的表达,同时 hnRNPU 稳定 c-MYC 的 mRNA。我们发现 hnRNPU 和 c-Myc 调节环对 HCC 的增殖和自我更新具有协同作用,并促进 HCC 的进展。总之,hnRNPU 作为 c-Myc 的新型转录靶标发挥作用,促进 HCC 的进展,可能成为治疗 c-Myc 驱动的 HCC 的有前途的靶点。

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