Small non-coding RNAs as therapeutic targets with delivery strategies in cancer treatment and their clinical applications

Recent advances in RNA biology have revealed unexpected diversity and complexity in RNA molecules and in cellular RNA metabolism. While protein-coding genes have taken center stage for decades, attention has significantly shifted toward the silent majority of the human genome, non-coding RNAs (ncRNAs). Aberrant ncRNA expression is closely linked to critical processes involved in cancer, including cell growth, proliferation, invasion, and metastasis. As such, ncRNAs represent promising targets for cancer therapy and are critical molecular markers for cancer prediction and prognosis, providing guidance for clinical decision-making. Small non-coding RNAs (sncRNAs), including microRNAs (miRNAs), small interfering RNAs (siRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), tRNA-derived small RNAs (tRNAs), and PIWI-interacting RNAs (piRNAs), arerdysregulatedarious cancers. These molecules can influence cancer progression through various mechanisms, including transcriptional and post-transcriptional modifications, epigenetics, and signal transduction pathways. Therefore, these small molecules hold significant promise as cancer biomarkers and potential therapeutic targets for cancer treatment. RNA technology offers promise as a therapeutic intervention for targeted gene silencing in cancer, and several RNA-based formulations are being evaluated in clinical trials for this purpose. Therefore, understanding the underlying molecular mechanisms of cancer development, identifying specific therapeutic targets, and developing effective drug delivery systems are essential. A deeper understanding of these mechanisms is also significant for the future development of RNA-targeted therapies. Carrier systems that facilitate the effective and safe delivery of small noncoding RNA-based therapeutics are crucial for successful clinical applications. RNA therapeutics must be delivered to the relevant organ and cell type and efficiently across the cell membrane to perform their intracellular functions. However, achieving therapeutic success requires a comprehensive understanding of the molecular mechanisms driving cancer, precise identification of therapeutic targets, and development of efficient and safe delivery systems for these agents.

This review examines the biogenesis of sncRNAs, their mechanisms of action, nanoformulation strategies, and studies focusing on sncRNA delivery systems. In addition, we present the cancer-fighting potential of RNA and RNA-related therapies and examine the current status of sncRNA therapeutics in the clinical trials.