Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu, China.
Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
Clin Sci (Lond). 2020 Jun 26;134(12):1457-1472. doi: 10.1042/CS20200244.
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 comprehensive 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.
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 个亚基组成，其中大多数亚基具有不同的作用，并且在 HCC 中经常异常表达。全面探索这些亚基的表达和临床意义将具有重要价值。在本研究中，我们从癌症基因组图谱 (TCGA) 中获得了每个 SWI/SNF 亚基的基因表达谱及其相应的临床信息。我们发现，与配对的正常肝组织相比，SWI/SNF 亚基中有 14 个在 HCC 组织中显著增加，其中 11 个亚基与总生存期 (OS) 显著相关。我们确定了一个由四个基因组成的预后标志，包括肌动蛋白样 6A (ACTL6A)、富含 AT 的相互作用域 1A (ARID1A)、SWI/SNF 相关、基质相关、肌动蛋白依赖性染色质调节剂亚家族 C 成员 1 (SMARCC1) 和 SWI/SNF 相关、基质相关、肌动蛋白依赖性染色质调节剂、亚家族 D、成员 1 (SMARCD1)，可有效预测 HCC 患者的 OS。在这些基因中，SMARCD1 具有最具预后价值。我们进一步进行了体外和体内实验，揭示了 SMARCD1 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 复合物亚基的表达，特别是 SMARCD1，与 HCC 的发展高度相关，并可作为有前途的预后预测因子。
