Comprehensive review and in silico analysis of the role of noncoding RNAs in retinoblastoma: A step-toward ncRNA precision.

Noncoding RNAs (ncRNAs) have greatly revolutionized our understanding of gene regulation and its main role in oncogenesis, particularly in retinoblastoma (RB), the most prevalent type of intraocular malignancy in children. Despite recent significant therapeutic advances, the prognosis for RB remains unclear owing to late diagnosis and resistance to conventional treatments. This review comprehensively explores the multiple roles of ncRNAs-microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs)-in RB pathogenesis. miRNA dysregulation serves as the initial cascade for modulating cell proliferation, apoptosis, and metastasis. Similarly, lncRNAs demonstrate dual behavior, functioning either as oncogenic drivers or tumor suppressors by interacting with several molecular targets and interacting with different signaling pathways, such as the PI3K/Akt and Wnt/β-catenin pathways. Additionally, circRNAs, owing to their persistent stability and unique ability to act as miRNA sponge main binding sites, affect various normal physiological processes, influencing tumor progression and chemoresistance. Emerging data also highlight the intricate crosstalk between piRNAs and other ncRNAs in retinal homeostasis and oncogenesis, with promising future implications for their utility as diagnostic biomarkers in liquid biopsy types. This comprehensive review consolidates the latest knowledge on the molecular mechanisms of noncoding RNAs (ncRNAs) in retinoblastoma (RB), along with in silico analysis of ncRNA-gene interactions, providing a guide for precision medical approaches. However, future research should aim to utilize ncRNAs as a vital clinical tool to improve the early diagnosis, prognosis, and targeted treatment of RB.