| Literature DB >> 31730895 |
Xiaolin Zhu1, Tingting Zhang1, Ye Zhang2, Hao Chen1, Jianbo Shen1, Xinxin Jin3, Jinhuan Wei4, Erhao Zhang4, Mingbing Xiao5, Yihui Fan6, Renfang Mao7, Guoxiong Zhou1.
Abstract
Pancreatic cancer is one of the most lethal malignant tumors due to a late diagnosis and highly invasion and metastasis. Transforming growth factor-β (TGF-β) signaling plays a vital role in the progression of pancreatic cancer. The delicate activity of TGF-β signaling is particular important for the development of aggression and metastasis which must be fine-tuned. Here, we investigated the role of super-enhancers in regulating the expression of TGF-β signaling pathway in pancreatic cancer. TGFBR2 owns the modification of H3K27Ac around the gene in pancreatic cancer cells. Inhibition of BRD4 by JQ1 robustly blocked the expression of TGFBR2 in a dose dependent manner. We successfully mapped a super-enhancer in TGFBR2 by sgRNA. Deletion of the super-enhancer in TGFBR2 (sgTGFBR2-SEΔ) significantly reduced the expression of TGFBR2 in pancreatic cancer cells. TGF-β-induced p-SMAD2/3 was greatly impaired in TGFBR2 super-enhancer deleted cells. Both migration and EMT induced by TGF-β in pancreatic cancer cells were impaired after deleting the super-enhancer of TGFBR2. Our data suggest a novel molecular mechanism by which a super-enhancer regulates TGFBR2, affecting the activity of TGF-β as well as its function in pancreatic cancer progression.Entities:
Keywords: Pancreatic cancer; Super-enhancer; TGF-β signaling; TGFBR2; Transcriptional regulation
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Year: 2019 PMID： 31730895 DOI： 10.1016/j.cellsig.2019.109470
Source DB: PubMed Journal: Cell Signal ISSN： 0898-6568 Impact factor: 4.315