Dark matter matters: from noncoding RNA regulation to cancer immunity

Long considered transcriptional noise, noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs (lncRNAs), are now recognized as central regulators of cellular function, acting as scaffolds, structural elements, and regulators of gene expression. This expanding functional landscape is reshaping our understanding of cancer biology, immune regulation, and the limits of translation itself. Beyond gene regulation, lncRNAs may be implicated in the earliest stages of oncogenic transformation, orchestrating molecular reprogramming and remodeling of the immune microenvironment in premalignant lesions. Their functional analysis has further exposed an unexpected translational dimension with some lncRNAs harboring open reading frames encoding micropeptides. These cryptic micropeptides constitute an underexplored dimension of the immunopeptidome that could shape T-cell development and antitumor immunity, with implications for cancer immunosurveillance and therapeutic targeting. Collectively, these findings call for a revised molecular dogma in which the noncoding genome is recognized as a major regulator of cellular function, oncogenic transformation, and immune surveillance.