Mitochondrial Long Non-Coding RNAs in Gynecological Cancers: Pathogenic Signaling Pathways and Therapeutic Opportunities

Understanding the complex molecular mechanisms behind gynecological cancers is crucial, as these diseases pose significant challenges to women's health and are frequently diagnosed at advanced stages. Various genetic, epigenetic, and metabolic alterations play a vital role in tumor development, metastasis, and therapy. Exploring mitochondrial dysfunction and the role of lncRNAs may provide essential insights into how tumor cells evade apoptosis, alter their metabolic pathways, and adapt to stress. In gynecological malignancies, nuclear lncRNAs contribute to tumor progression, treatment resistance, and metastasis through mechanisms that include chromatin remodeling, microRNA modulation, and regulation of mitochondrial dynamics. More recently, the emerging role of mt-lncRNAs, derived from the mitochondrial genome, has attracted attention for their involvement in retrograde signaling, mitochondrial respiration, and regulation of apoptosis. Dysregulation of mt-ncRNAs may contribute to tumor bioenergetic reprogramming, mitochondrial integrity, and nuclear gene expression. The objective of this review is to consolidate the current understanding of the regulatory mechanisms of mitochondrial lncRNAs in ovarian, cervical, and endometrial cancers, thus identifying new opportunities of research. A thorough elucidation of the role of mitochondrial lncRNAs in mitochondrial-nuclear communication may facilitate the development of new interventions in gynecological oncology, highlighting the potential of these molecules as diagnostic biomarkers and therapeutic targets.