Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma

作者：Jiong Li, Wendi Wang, Sang Li, Zhengkang Qiao, Haoyue Jiang, Xinyue Chang, Ya-Ning Zhu, Hongpei Tan, Xiaoqian Ma, Yuqian Dong, Zhenhu He, Zhen Wang, Qin Liu, Shanhu Yao, Cejun Yang, Min Yang, Lu Cao, Juan Zhang, Wei Li, Wei Wang, Zhe Yang, Pengfei Rong · 发表于：Cancer Cell International · 年份：2024 · DOI：10.1186/s12935-024-03353-x · 被引用次数：12 · 研究领域：RNA Research and Splicing、TGF-β signaling in diseases、Cytokine Signaling Pathways and Interactions

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-β signaling pathway may be associated with tumor progression. However, the relationship between TGF-β signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-β signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could ...