Enhanced SMARCD1, a subunit of the SWI/SNF complex, promotes liver cancer growth through the mTOR pathway
Enhanced SMARCD1, a subunit of the SWI/SNF complex, promotes liver cancer growth through the mTOR pathway
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增强型 SMARCD1（SWI/SNF 复合物的一个亚基）通过 mTOR 途径促进肝癌生长
DOI：
10.1042/cs20200244
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发表时间：
2020-06-01
期刊：
影响因子：
6
通讯作者：
Bu, Hong
中科院分区：
文献类型：
--
作者：
Zhou, Yongjie;Xu, Qing;Bu, Hong
染色质重塑复合物SWI/SNF调节靶基因对转录因子的可及性，在肝细胞癌（HCC）的发生中起着关键作用。SWI/SNF复合物由大约15个亚基组装而成，并且这些亚基中的大多数具有不同的作用，并且通常在HCC中异常表达。深入探讨这些亚基的表达及其临床意义具有重要价值。在本研究中，我们从癌症基因组图谱（TCGA）中获得了每个SWI/SNF亚基的基因表达谱和相应的临床信息。我们发现15个SWI/SNF亚基中有14个在肝癌组织中显著高于配对的正常肝组织，11个亚基与总生存期（OS）显著相关。我们确定了一个四基因预后标志，包括肌动蛋白样6A（ACTL 6A），AT丰富的相互作用结构域1A（ARID 1A），SWI/SNF相关的，基质相关的，染色质亚家族C成员1的肌动蛋白依赖性调节因子（SMARCC 1）和SWI/SNF相关的，基质相关的，染色质亚家族D，成员1的肌动蛋白依赖性调节因子（SMARCD 1），可以有效地预测肝癌患者的OS。在这些基因中，SMARCD 1具有最大的预后价值。我们进一步进行了体外和体内实验，并揭示了SMARD 1通过激活mTOR信号通路促进肝癌生长。总之，我们的研究表明，SWI/SNF复合物亚基，特别是SMARD 1的表达与HCC的发展高度相关，并作为一个有前途的预后预测因子。
The chromatin remodeling complex SWI/SNF regulates the accessibility of target genes to transcription factors and plays a critical role in the tumorigenesis of hepatocellular carcinoma (HCC). The SWI/SNF complex is assembled from approximately 15 subunits, and most of these subunits have distinct roles and are often aberrantly expressed in HCC. A compre-hensive exploration of the expression and clinical significance of these subunits would be of great value. In the present study, we obtained the gene expression profile of each SWI/SNF subunit and the corresponding clinical information from The Cancer Genome Atlas (TCGA). We found that 14 out of the 15 SWI/SNF subunits were significantly increased in HCC tissues compared with paired normal liver tissues, and 11 subunits were significantly associated with overall survival (OS). We identified a four-gene prognostic signature including actin-like 6A (ACTL6A), AT-rich interaction domain 1A (ARID1A), SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily C member 1 (SMARCC1) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily D, member 1 (SMARCD1) that could effectively predict OS in HCC patients. Among the genes, SMARCD1 has the most prognostic value. We further conducted in vitro and in vivo experiments and revealed that SMARCD1 promotes liver cancer growth by activating the mTOR signaling pathway. In conclusion, our study has revealed that the expression of SWI/SNF complex subunits, especially SMARCD1, is highly associated with HCC development and acts as a promising prognostic predictor.