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Twist1-YY1-p300 complex promotes the malignant progression of HCC through activation of miR-9 by forming phase-separated condensates at super-enhancers and relieved by metformin.
- Source :
-
Pharmacological Research . Feb2023, Vol. 188, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- 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. [Display omitted] [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10436618
- Volume :
- 188
- Database :
- Academic Search Index
- Journal :
- Pharmacological Research
- Publication Type :
- Academic Journal
- Accession number :
- 161767631
- Full Text :
- https://doi.org/10.1016/j.phrs.2023.106661