A Synopsis on the Role of Long Non-coding RNA during Arsenic-associated Urinary Bladder Carcinogenesis and its Potential as an Early-detection Biomarker

Urinary bladder cancer (BLCA) is the most prevalent urothelial cancer and is notably more common in men, likely due to prolonged exposure to risk factors and androgens. The standard classification divides BLCA into non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder Cancer (MIBC) based on the extent of tumor infiltration into the bladder epithelium. Environmental arsenic exposure, prevalent in several pockets of the world, including India, is a key etiological factor besides tobacco, contributing to BLCA development. Chronic arsenic exposure causes oxidative DNA damage, genomic instability, and epigenetic changes, affecting various signaling pathways and driving cellular immortality and proliferation. Certain aberrations are emerging as potential biomarkers for early diagnosis and prognosis of BLCA, offering more specificity and precision compared to conventional cystoscopy and biopsy. Recent studies have highlighted long non-coding RNAs (lncRNAs) associated with all cancer hallmarks. Their tissue and disease specificity, along with their stability and availability, make them promising biomarkers. In this review, we discussed gene mutations, copy number variations in genetic loci (such as 12q13-26, 11p15.5, 12q13.13, 8q24.21, 9p21.5-24.3, 18q11.1-26, 9p21.11-9p33.3, 6p25.3-27, 5q11.1-35.3, and 14q11.2) and differentially regulated pathways, especially with arsenic-associated BLCA. These chromosomal regions also harbor genes for differentially regulated lncRNAs. Hence, we shed light on the potential of the lncRNAs as biomarkers to facilitate quicker and easier detection of arsenic-related BLCA, preferably through non-invasive means.