Post-transcriptional Regulation in Cancer Dormancy: An Underappreciated Regulatory Layer

Cancer dormancy is a clinically silent state in which residual tumor cells persist without overt tumor growth and serve as a reservoir for late metastatic recurrence. Although extrinsic niche-derived cues and intrinsic transcriptional programs governing dormancy have been extensively studied, post-transcriptional regulation has emerged as an important yet underappreciated layer controlling dormancy entry, maintenance, and metastatic reactivation. In this review, we provide an integrated overview of the multilayered regulatory networks that govern cancer dormancy, beginning with niche-derived signaling, extracellular matrix remodeling, mechanotransduction, and immune surveillance, which collectively establish and maintain the dormant state. We then focus on the emerging landscape of RNA-mediated post-transcriptional regulation, highlighting how microRNAs, long non-coding RNAs, circular RNAs, and RNA-binding proteins cooperatively regulate cell-cycle arrest, metabolic adaptation, immune evasion, therapy resistance, and metastatic reactivation. Collectively, this review provides a comprehensive perspective on the molecular basis of tumor persistence and metastatic recurrence and establishes a conceptual framework for identifying potential therapeutic targets to prevent metastatic relapse.