Altered mRNA expression levels of the major components of sphingolipid metabolism, ceramide synthases and their clinical implication in colorectal cancer

Abstract

Ceramide synthases (CerSs) synthesize various ceramides of different acyl chain lengths and serve important roles in the proliferation and death of cancer cells by regulating sphingolipid metabolism-related signaling pathways. The present study investigated the mRNA expression levels of various CerS genes using mRNA expression data from six independent colorectal cancer (CRC) cohorts and a Korean CRC dataset. Expression levels of CERS2, CERS5 and CERS6 mRNA were significantly increased in the majority of the studied groups. However, CERS4 expression was only significantly altered in two groups. Additionally, a positive correlation was observed between altered CERS4 and CERS5 mRNA levels in The Cancer Genome Atlas Colon and Rectal Cancer dataset. Notably, CERS2 and CERS4, as well as CERS5 and CERS6 levels, were positively correlated with each other in Korean patients with CRC. However, the mRNA expression levels of these four CerS genes were not associated with any clinicopathological characteristics in Korean patients with CRC. Finally, overexpressing CERS2 or CERS6 inhibited the in vitro viability of various CRC cells. Taken together, these findings indicated that CERS2, CERS4, CERS5, and CERS6 are significantly dysregulated in CRC, suggesting they may serve important roles in the pathophysiology of this malignancy.

Bioinformatic Exploration for Prognostic Significance of Sphingolipid Metabolism-Related Genes in Invasive Ductal Carcinoma Using the Cancer Genome Atlas Cohort

“… 9 Moreover, significant correlations between LASS2 and LASS4 , and between LASS5 and LASS4 / LASS6 were identified in various colorectal cancer cohorts. 31 Interestingly, in the present study, only the correlation between LASS2 and LASS3 was significant in female IDC ( Table 3 ).…”

In Silico Analysis for Sphingolipid Metabolism-Related Genes in Human Kidney Clear Cell Carcinoma Using The Cancer Genome Atlas.

“…Significant correlations between the sphingolipid metabolism-related genes have been reported in various CRC cohorts, including CERS2 and CERS4, CERS4 and CERS5, and CERS5 and CERS6 [33]. Inter-individual correlations between the significantly dysregulated sphingolipid metabolism-related genes of ccRCC revealed 69 significant correlations; however, no genes were correlated with these six CERS genes as none of these genes showed significantly-altered expression levels in ccRCC compared with those in NST.…”

The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy

“…CerS2 overexpression in MDA-MB-231 breast cancer cells was shown to decrease cell migration and invasion, and CerS2 expression was associated with improved patient survival in breast, ovarian, lung, and liver cancer [65,79]. CerS5 has been noted to be upregulated in colorectal cancer and was associated with poor patient survival and 5-year cancer recurrence [73,80,81]. CerS5 has also been noted to be a biomarker for colorectal cancer [81].…”