RP11-Derived Long Non-Coding RNAs in Hepatocellular Carcinoma: Hidden Treasures in Plain Sight

Hepatocellular carcinoma (HCC) remains one of the most prevalent and lethal malignancies worldwide. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of gene expression and cancer progression, yet the functional diversity of RP11-derived lncRNAs-originally mapped to bacterial artificial chromosome (BAC) clones from the Roswell Park Cancer Institute-has only recently begun to be appreciated. This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC, outlining their genomic origins, molecular mechanisms, and biological significance. We highlight their roles in metabolic reprogramming, microRNA network modulation, and tumor progression, as well as their diagnostic and prognostic value in tissue and serum-based analyses. Finally, we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.