Predictive significance of glycolysis-associated lncRNA profiles in colorectal cancer progression.

ABSTRACT

BACKGROUND: The Warburg effect is a hallmark characteristic of colorectal cancer (CRC). Despite extensive research, the role of long non-coding RNAs (lncRNAs) in influencing the Warburg effect remains incompletely understood. Our study aims to identify lncRNAs that may modulate the Warburg effect by functioning as competing endogenous RNAs (ceRNAs). METHODS: Utilizing bioinformatics approaches, we extracted glycolysis-associated gene data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-related lncRNAs in CRC. We employed Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and Multivariable Cox regression to develop a prognostic model comprising four glycolysis-linked lncRNAs. We then constructed a prognostic nomogram integrating this lncRNA model with other relevant clinical parameters. RESULTS: The prognostic efficacy of our four-lncRNA signature and its associated nomogram was validated in both training and validation cohorts. Functional assays demonstrated significant glycolysis and hexokinase II (HK2) inhibition following the silencing of RUNDC3A - AS1, a key lncRNA in our prognostic signature, highlighting its regulatory importance in the Warburg effect. CONCLUSIONS: Our research illuminates the critical role of glycolysis-centric lncRNAs in CRC. The developed prognostic model and nomogram underscore the pivotal prognostic and regulatory significance of the lncRNA RUNDC3A - AS1 in the Warburg effect in colorectal cancer.