Regulation of Different Types of Cell Death by Noncoding RNAs: Molecular Insights and Therapeutic Implications

Abstract

Noncoding RNAs (ncRNAs) are crucial regulatory molecules in various biological processes, despite not coding for proteins. ncRNAs are further divided into long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) based on the size of their nucleotides. These ncRNAs play crucial roles in transcriptional, post-transcriptional, and epigenetic regulation. The regulatory roles of noncoding RNAs, including lncRNAs, miRNAs, and circRNAs, are essential in various modalities of cellular death, such as apoptosis, ferroptosis, cuproptosis, pyroptosis, disulfidptosis, and necroptosis. These noncoding RNAs are integral to modulating gene expression and protein functionality during cellular death mechanisms. In apoptosis, lncRNAs, miRNAs, and circRNAs influence the transcription of apoptotic genes. In ferroptosis, these noncoding RNAs target genes and proteins involved in iron homeostasis and oxidative stress responses. For cuproptosis, noncoding RNAs regulate pathways associated with the accumulation of copper ions, leading to cellular death. During pyroptosis, noncoding RNAs modulate inflammatory mediators and caspases, affecting the proinflammatory cell death pathway. In necroptosis, noncoding RNAs oversee the formation and functionality of necrosomes, thereby influencing the balance between cellular survival and death. Disulfidptosis is a unique type of regulated cell death caused by the excessive formation of disulfide bonds within cells, leading to cytoskeletal collapse and oxidative stress, especially under glucose-limited conditions. This investigation highlights the complex mechanisms through which noncoding RNAs coordinate cellular death, emphasizing their therapeutic promise as potential targets, particularly in the domain of cancer treatment.