Construction and analysis of the CDKN2B-AS1 ceRNA network associated with KRAS-dependent tumorigenesis in colorectal and pancreatic cancer

Kirsten rat sarcoma viral oncogene homolog (KRAS) exhibits the highest mutation rate in colorectal cancer (CRC) and pancreatic cancer (PC), highlighting the need for a comprehensive understanding of KRAS-dependent pathogenesis. Given the regulatory role of long noncoding RNAs (lncRNAs) in gene expression, this study focused on constructing a competing endogenous RNA (ceRNA) network of selected KRAS-related lncRNAs. By analyzing the transcriptional profiles of CRC and PC cell lines with and without KRAS mutations, differentially expressed genes (DEGs) were identified using sequencing data from the Sequencing Read Archive database. Notably, the analysis revealed 42 common upregulated DEGs (uDEGs), including differentially expressed lncRNAs and protein-coding genes, between KRAS-mutant and KRAS-wild-type cells. Among them, CDKN2B-AS1 emerged as a key KRAS-related lncRNA for the construction of the ceRNA network. Using LncTarD, miRWalk, and ToppCluster servers, a robust ceRNA network of CDKN2B-AS1 was constructed to elucidate the interactions between corresponding miRNAs and target genes. This network included 21 miRNAs and 34 genes selected from common uDEGs. Enrichment analysis of ceRNA target genes validated their involvement in critical cancer-related pathways and biological processes. Crucially, expression and survival analysis underscored the prognostic significance of selected target genes within the CDKN2B-AS1 ceRNA network. By delineating the regulatory mechanisms of the CDKN2B-AS1 ceRNA network, this study sheds light on the molecular and cellular pathways involved in KRAS-associated tumorigenesis.