Kumari Reshmi, Banerjee Satarupa
Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India.
ACS Pharmacol Transl Sci. 2025 Apr 30;8(5):1205-1226. doi: 10.1021/acsptsci.4c00681. eCollection 2025 May 9.
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.
非编码RNA（ncRNAs）是各种生物过程中的关键调节分子，尽管它们不编码蛋白质。根据核苷酸大小，ncRNAs进一步分为长链非编码RNA（lncRNAs）、微小RNA（miRNAs）和环状RNA（circRNAs）。这些ncRNAs在转录、转录后和表观遗传调控中发挥关键作用。包括lncRNAs、miRNAs和circRNAs在内的非编码RNA的调节作用在细胞死亡的各种形式中至关重要，如凋亡、铁死亡、铜死亡、焦亡、二硫键介导的细胞死亡和坏死性凋亡。这些非编码RNA在细胞死亡机制中对于调节基因表达和蛋白质功能不可或缺。在凋亡过程中，lncRNAs、miRNAs和circRNAs影响凋亡基因的转录。在铁死亡过程中，这些非编码RNA靶向参与铁稳态和氧化应激反应的基因和蛋白质。对于铜死亡，非编码RNA调节与铜离子积累相关的途径，导致细胞死亡。在焦亡过程中，非编码RNA调节炎症介质和半胱天冬酶，影响促炎细胞死亡途径。在坏死性凋亡过程中，非编码RNA监督坏死小体的形成和功能，从而影响细胞存活与死亡之间的平衡。二硫键介导的细胞死亡是一种独特的程序性细胞死亡类型，由细胞内二硫键过度形成引起，导致细胞骨架塌陷和氧化应激，特别是在葡萄糖受限的条件下。本研究强调了非编码RNA协调细胞死亡的复杂机制，强调了它们作为潜在靶点的治疗前景，特别是在癌症治疗领域。
