Clinical and Biological Significance of Sodium Channel Modifier 1 as a Component of the Minor Spliceosome in Hepatocellular Carcinoma.

Abstract

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. The progression of HCC involves complex molecular mechanisms, including chromosomal amplification and alterations in pre-mRNA splicing. In this study, we investigated sodium channel modifier 1 (SCNM1), a component of the minor spliceosome, as a potential oncogenic driver of HCC.

Methods: We analyzed SCNM1 expression and its relationship with clinical outcomes using The Cancer Genome Atlas and GSE14520 datasets and patient samples. Functional assays, including realtime-quantitative polymerase chain reaction, Western blotting, colony formation, and apoptosis analyses, were performed to elucidate the role of SCNM1 in HCC progression. We also evaluated the correlations between SCNM1 and its downstream targets DERL2 and BAG6.

Results: Because of DNA copy number gain and arm-level amplification of chromosome 1q, SCNM1 expression was significantly elevated in HCC tissues. High SCNM1 expression correlated with poor prognosis and was identified as an independent prognostic factor. Via its splicing activity, SCNM1 promotes tumor growth, suppresses apoptosis, and regulates the expressions of DERL2 and BAG6, which contribute to cancer cell survival by facilitating protein degradation and suppressing apoptosis. Overexpression of SCNM1 is observed in multiple cancer types, suggesting a broad oncogenic role.

Conclusions: Sodium channel modifier 1 plays a critical role in HCC progression by regulating the key pathways involved in tumor proliferation and survival. Its restricted expression in specific cancer types and influence on the minor spliceosome highlights its potential as a cancer-specific therapeutic target. Further research on SCNM1-targeted therapies may provide innovative strategies for treating HCC and other cancers.