Expression Alterations and Functions of Long Non-Coding RNAs in Retinoblastoma

Abstract Retinoblastoma (RB) is the leading intraocular malignancy in childhood, primarily resulting from the inactivation of the Rb genes. This disease predominantly affects children under the age of ۵ years. Annually, approximately ۹,۰۰۰ new pediatric cases of RB are diagnosed, significantly impacting the quality of life for affected infants. Although treatment strategies such as ophthalmectomy, chemotherapy, cryotherapy, and laser therapy have improved clinical outcomes, mortality rates remain as high as ۷۰% in underdeveloped regions, largely attributed to tumor invasion and metastasis. Recent studies indicate that gene mutations and alterations in expression levels contribute to the initiation and progression of RB. Long non-coding RNAs (lncRNAs), which are RNA molecules longer than ۲۰۰ nucleotides, play crucial roles in various biological processes, including the regulation of gene expression. In oncology, lncRNAs have emerged as important players in the pathogenesis of multiple cancers, including RB, and may serve as potential biomarkers or therapeutic targets. Retinoblastoma is associated with the biallelic inactivation of the Rb۱ gene, a critical tumor suppressor located on chromosome ۱۳ at the ۱۳q۱۴ region. Mutations in this gene can be hereditary or non-hereditary, leading to familial or sporadic cases of RB. Hereditary RB often presents earlier in life and is typically characterized by both alleles being affected, whereas non-hereditary cases exhibit a single mutation. The Rb۱ gene is also implicated in various epigenetic alterations that control gene expression and chromatin dynamics. Alterations such as DNA methylation, histone modifications, and changes in non-coding RNA expression can influence tumor progression in RB. In this study, we investigate the expression, alterations, and functional roles of lncRNAs in retinoblastoma. These lncRNAs—AFAP۱-AS۱, BANCR, NEAT۱, CCAT۱, and XIST—are strongly linked to the progression and malignancy of retinoblastoma. They hold promise for clinical application as prognostic markers, diagnostic tools, or potential targets for therapeutic intervention. ANRIL, PlncRNA-۱, HOTAIR, PANDAR, DANCR, PVT۱, LINC۰۰۲۰۲, and THOR illustrate critical roles in the oncogenesis of retinoblastoma by modulating various signaling pathways, gene expression, and cellular processes. Their functions as regulators of cancer progression and potential therapeutic targets represent significant areas for further research and clinical exploration in the treatment of retinoblastoma. The exploration of downregulated lncRNAs, such as MEG۳, MT۱JP, BDNF-AS, and H۱۹, in retinoblastoma is significant, as these molecules not only enhance our understanding of the molecular underpinnings of the disease but also present avenues for the development of innovative diagnostic and therapeutic strategies. MEG۳ is recognized as a tumor suppressor in various cancers, including retinoblastoma, and plays critical roles in inhibiting cell proliferation and promoting apoptosis. MT۱JP is associated with several cancer hallmark properties and acts as a regulator of the p۵۳ signaling pathway. In the context of retinoblastoma, H۱۹ appears to assume an anti-tumorigenic function. BDNF-AS is downregulated in RB, and when its expression is restored, it has been shown to inhibit cell cycle progression and suppress RB development, indicating its potential as a prognostic marker.

کلیدواژه ها:

Retinoblastoma ، Long non-coding RNA(LncRna) ، prognostic markers ، tumor suppressor ، gene expression