增强子
肝细胞癌
YY1年
癌症研究
转录因子
肿瘤进展
癌症
抄写(语言学)
生物
基因表达
医学
基因
内科学
发起人
遗传学
哲学
语言学
作者
Jing Meng,Jing Han,Xiaorui Wang,Ting Wu,Heng Zhang,Huihui An,Lu-Ning Qin,Yu Sun,Weilong Zhong,Cheng Yang,Huijuan Liu,Tao Sun
标识
DOI:10.1016/j.phrs.2023.106661
摘要
Hepatocellular carcinoma (HCC) is one of the leading causes of death, which deserves further study to reveal the underlying molecular mechanisms. Studies have shown that miR-9 in associated with poor prognosis in HCC patients. However, the mechanisms of transcriptional activation regulation of miR-9 and its role in the malignant progression of HCC have been rarely investigated. Some transcriptional coactivators can form phase-separated condensates at super-enhancers that compartmentalize and concentrate the transcription apparatus to drive robust gene expression. Here, we demonstrate that Twist1 and YY1 could form a transcriptional complex with p300, creating local high-concentration phase-separated interaction hubs at the super-enhancers of miR-9 and activate its expression to promote the malignant progression of HCC by stimulating the migration and invasion of hepatocellular carcinoma cells. Twist1-YY1-p300 phase-separated condensates were disrupted by metformin (Met) and thus reduce miR-9 expression, thereby inhibiting the malignant progression of HCC. Our study demonstrates that the Twist1 transcriptional factor complex involved in the malignant progression of HCC can form phase separation condensates at super-enhancers of miR-9 to promote the expression of oncogenes in HCC cells. It provides a potential target for the therapy of HCC and offers insights into the mechanism of Met in HCC inhibition.
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