Attenuated expression of SNF5 facilitates progression of bladder cancer via STAT3 activation.
Attenuated expression of SNF5 facilitates progression of bladder cancer via STAT3 activation.
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SNF5 表达减弱通过 STAT3 激活促进膀胱癌的进展。
DOI：
10.1186/s12935-021-02363-3
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发表时间：
2021-12-07
影响因子：
5.8
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Ding H;Huang Y;Shi J;Wang L;Liu S;Zhao B;Liu Y;Yang J;Chen Z
SWI/SNF是一种众所周知的ATP依赖性染色质复合物，在几种生物过程中起着至关重要的作用。 SNF5是SWI/SNF重塑复合物的核心亚基，在95％的恶性胸腺肿瘤（MRT）中灭活，突出了其在肿瘤发生中的重要性。但是，SNF5在膀胱癌（BC）中的作用仍然未知。在这项研究中，我们旨在研究SNF5在BC中的功能和潜在临床适用性。
来自癌症基因组图集（TCGA），基因表达综合（GEO）和癌细胞系百科全书（CCLE）数据库的数据用于评估BC中SNF5的临床意义。我们进行了基因集富集分析（GSEA）和功能测定，以研究SNF5在BC中的作用。进行了药物敏感性的基因组学（GDSC）和药物敏感性测试，以确定SNF5在BC治疗中的潜在值。
SNF5低表达赋予了较差的预后，并且与卑诗省的N阶段显着相关。 ROC曲线表明SNF5可以将BC与正常组织区分开。体外和体内功能分析表明，减弱的SNF5表达可以促进细胞增殖并通过Stat3激活增强迁移。我们认为，低SNF5表达可以赋予对常规一线药物的更大耐药性，包括卑诗省的顺铂和吉西他滨。 GDSC和药物抗性测定法表明，低SNF5表达使T24和5637细胞对EGFR抑制剂吉非替尼高敏感，以及EZH2抑制剂GSK126和顺铂的组合。
据我们所知，本研究首次表明，低SNF5表达可以通过激活STAT3并赋予卑诗省预后不良来促进细胞增殖和迁移。重要的是，SNF5表达可能是确定可以从EGFR靶向化疗或顺铂与EZH2抑制剂治疗方案结合使用的BC患者的有前途的候选人。
在线版本包含的补充材料可获得10.1186/s12935-021-02363-3。
SWI/SNF, a well-known ATP-dependent chromatin-remodeling complex, plays an essential role in several biological processes. SNF5, the core subunit of the SWI/SNF remodeling complex, inactivated in 95% of malignant rhabdoid tumors (MRT), highlighting its significance in tumorigenesis. However, the role of SNF5 in bladder cancer (BC) remains unknown. In this study, we aimed to investigate the function and potential clinical applicability of SNF5 in BC. Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were used to evaluate the clinical significance of SNF5 in BC. We performed Gene Set Enrichment Analysis (GSEA) and functional assays to investigate the role of SNF5 in BC. Genomics of Drug Sensitivity in Cancer (GDSC) and drug-susceptibility tests were performed to identify the potential value of SNF5 in the treatment of BC. Low SNF5 expression conferred a poor prognosis and was significantly associated with the N-stage in BC. ROC curves indicated that SNF5 could distinguish BC from the normal tissues. In vitro and in vivo functional assays demonstrated that attenuated SNF5 expression could promote cell proliferation and enhance migration by STAT3 activation. We imputed that low SNF5 expression could confer greater resistance against conventional first-line drugs, including cisplatin and gemcitabine in BC. GDSC and drug-resistance assays suggested that low SNF5 expression renders T24 and 5637 cells high sensitivity to EGFR inhibitor gefitinib, and combination of EZH2 inhibitor GSK126 and cisplatin. To the best of our knowledge, the present study, for the first time, showed that low SNF5 expression could promote cell proliferation and migration by activating STAT3 and confer poor prognosis in BC. Importantly, SNF5 expression may be a promising candidate for identifying BC patients who could benefit from EGFR-targeted chemotherapy or cisplatin in combination with EZH2 inhibitor treatment regimens. The online version contains supplementary material available at 10.1186/s12935-021-02363-3.
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