No.8 District of Liver Diseases, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China.
Clinical Laboratory, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China.
Yonsei Med J. 2021 Dec;62(12):1073-1082. doi: 10.3349/ymj.2021.62.12.1073.
The purpose of this study was to investigate the influences of sex comb on midleg like-2 (SCML2) on hepatocellular carcinoma (HCC) and potentially related mechanisms.
SCML2 expression in tumor tissues and cells was analyzed using the TCGA database and/or qRT-PCR. The proliferation of HCC cells was detected by CCK-8, colony formation, and EdU assays. The migration and invasion of HCC cells were detected by transwell and wound healing assays. Apoptosis of HCC cells was determined by flow cytometry. Additionally, qRT-PCR and Western blot were used to detect the expression of SCML2 and Wnt/β-catenin/epithelial-mesenchymal transition (EMT) signaling. A xenograft model in mice was established to verify the in vitro findings.
We found that SCML2 was highly expressed in HCC tissues and cells and that high expression of SCML2 was correlated with poor prognosis in HCC patients. SCML2 overexpression promoted proliferation, invasion, and migration and repressed apoptosis of HCC cells. The reverse results were obtained in SCML2-silenced cells. Further, we found that SCML2 activated the Wnt/β-catenin/EMT pathway. SCML2 silencing reduced the protein levels of Wnt3a, β-catenin, N-cadherin, Vimentin, and Snail and enhanced E-cadherin protein expression both in vivo and in vitro.
SCML2 silencing inhibits the proliferation, migration, and invasion of HCC cells by regulating the Wnt/β-catenin/EMT pathway.
本研究旨在探讨性梳中间腿样 2(SCML2)对肝细胞癌(HCC)的影响及其潜在相关机制。
利用 TCGA 数据库和/或 qRT-PCR 分析肿瘤组织和细胞中 SCML2 的表达。通过 CCK-8、集落形成和 EdU 检测分析 HCC 细胞的增殖。通过 Transwell 和划痕愈合检测分析 HCC 细胞的迁移和侵袭。通过流式细胞术检测 HCC 细胞的凋亡。此外,通过 qRT-PCR 和 Western blot 检测 SCML2 和 Wnt/β-catenin/上皮间质转化(EMT)信号的表达。建立小鼠异种移植模型以验证体外发现。
我们发现 SCML2 在 HCC 组织和细胞中高表达,且 SCML2 高表达与 HCC 患者的不良预后相关。SCML2 过表达促进 HCC 细胞的增殖、侵袭和迁移,抑制细胞凋亡。在 SCML2 沉默的细胞中则得到相反的结果。进一步研究发现,SCML2 激活了 Wnt/β-catenin/EMT 通路。SCML2 沉默在体内和体外均降低了 Wnt3a、β-catenin、N-钙黏蛋白、波形蛋白和 Snail 的蛋白水平,增强了 E-钙黏蛋白的蛋白表达。
SCML2 沉默通过调节 Wnt/β-catenin/EMT 通路抑制 HCC 细胞的增殖、迁移和侵袭。