Predictive Significance of Glycolysis-Associated lncRNA Profiles in Colorectal Cancer Progression

Abstract

Abstract Background The Warburg effect constitutes a signature characteristic of colorectal cancer (CRC). Although there have been extensive investigations in the past, the implications of long non-coding RNAs (lncRNAs) in modulating the Warburg effect are still not fully elucidated. Our research primarily focuses on uncovering lncRNAs that potentially regulate the Warburg effect by acting as competing endogenous RNAs (ceRNAs). Methods We sourced glycolysis-associated genes from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-linked lncRNAs in CRC via bioinformatics techniques. Through a combination of Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and multivariable Cox regression evaluations, we designed a prognostic model consisting of four distinct glycolysis-related lncRNAs. Subsequently, a prognostic nomogram was conceived integrating the glycolysis-associated lncRNA model and other pertinent clinical parameters. Results The robust prognostic efficacy of the quartet glycolysis-related-lncRNA signature and the corresponding nomogram was corroborated across both training and validation cohorts. Functional assays revealed a notable suppression in glycolysis and hexokinase II (HK2) expression upon silencing lncRNA RUNDC3A − AS1, a pivotal lncRNA within our prognostic signature. This underscores the significant regulatory role of lncRNA RUNDC3A − AS1 in the Warburg effect. Conclusions We have successfully highlighted glycolysis-centric lncRNAs in CRC. Through our prognostic model and nomogram, we accentuated the lncRNA RUNDC3A − AS1's crucial prognostic and regulatory role in the Warburg effect within colorectal cancer cells.