Yonsei Med J.  2021 Dec;62(12):1073-1082. 10.3349/ymj.2021.62.12.1073.

Sex Comb on Midleg Like-2 Accelerates Hepatocellular Carcinoma Cell Proliferation and Metastasis by Activating Wnt/β-Catenin/EMT Signaling

• Du L
• Wang L
• Yang H
• Duan J
• Lai J
• Wu W
• Fan S
• Zhi X

• KMID: 2522581
• DOI: http://doi.org/10.3349/ymj.2021.62.12.1073

Abstract

Purpose
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.
Materials and Methods
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.
Results
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.
Conclusion
SCML2 silencing inhibits the proliferation, migration, and invasion of HCC cells by regulating the Wnt/β-catenin/ EMT pathway.

Keyword

Sex comb on midleg like-2; hepatocellular carcinoma; proliferation; apoptosis; signaling pathway