Research progress on the regulation of cuproptosis-related genes by non-coding RNAs in tumors

Abstract Cuproptosis represents a mechanistically distinct programmed cell death pathway divergent from canonical apoptosis, necrosis, and ferroptosis. This copper-dependent process critically modulates tumorigenesis, malignant progression, and clinical outcomes in neoplastic diseases. Non-coding RNAs (ncRNAs) modulate the expression of cuproptosis-related genes (CRGs) in tumors through the competing endogenous RNA mechanism. This regulation leads to copper ion accumulation, oxidative stress response, protein lipoylation, and ubiquitin-proteasome system activation, which eventually inhibit the occurrence and progression of tumors. The modulation of CRG expression by ncRNAs offers new perspectives for precision-targeted cancer therapy. This could potentially help develop more accurate and effective treatment approaches. Here, we review the mechanisms underlying cuproptosis, summarize the regulatory roles of ncRNAs in tumors, analyze the expression patterns of CRGs across multiple cancer types and their impact on patient prognosis, and elucidate the molecular mechanisms by which ncRNAs regulate cuproptosis in tumors. Furthermore, we provide clinical perspectives and highlight the potential opportunities for developing innovative therapeutic strategies for cancer.