The immunoregulatory role of lncRNA UCA1: a pan-cancer perspective with a focus on colorectal cancer

Abstract

Long non-coding RNA UCA1 has emerged as a critical regulator in cancer biology. This study comprehensively investigates UCA1 expression and its functional relevance across multiple cancer types, with a focus on colorectal cancer (CRC). Pan-cancer analyses were conducted using data retrieved from TCGA, GTEx, cBioPortal, and BEST databases, integrated via R programming. Single-cell RNA sequencing data from CellxGene platform were used to explore cell-type-specific UCA1 expression. Functional enrichment, co-expression networks, genomic alterations, diagnostic profile, CpG methylation, immune associations, and drug response profiles as well as experimental validation were also assessed. UCA1 was significantly overexpressed in at least 10 tumor types, most notably in CRC. Single-cell analysis revealed UCA1 expression across epithelial, stromal, and immune cell populations, including T cells and plasma cells. UCA1 correlated with genes like GRHL3 and KLK8, implicating roles in tissue development, adhesion, and motility. Genomic analyses revealed copy number amplifications (e.g., 17q12) and altered methylation patterns. Elevated UCA1 expression was linked to poorer prognosis in several cancers and positively correlated with recurrence and progression risk in CRC and other tumors. Immune analysis showed UCA1's association with regulatory T cells, chemokines, and immune checkpoints, indicating an immunosuppressive role. Additionally, UCA1 impacted drug resistance and sensitivity across therapies. UCA1 plays a multifaceted role in cancer progression, immune modulation, and therapy response. Its expression in diverse cell types within the tumor microenvironment and association with clinical outcomes supports its potential as a prognostic biomarker and therapeutic target, especially in CRC.