Non-coding RNAs in ferroptotic cancer cell death pathway: meet the new masters

Despite the recent advances in cancer therapy, cancer chemoresistance looms large along with radioresistance, a major challenge in dire need of thorough and minute investigation. Not long ago, cancer cells were reported to have proven refractory to the ferroptotic cell death, a newly discovered form of regulated cell death (RCD), conspicuous enough to draw attention from scholars in terms of targeting ferroptosis as a prospective therapeutic strategy. However, our knowledge concerning the underlying molecular mechanisms through which cancer cells gain immunity against ferroptosis is still in its infancy. Of late, the implication of non-coding RNAs (ncRNAs), including circular RNAs (circRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) in ferroptosis has been disclosed. Nevertheless, precisely explaining the molecular mechanisms behind the contribution of ncRNAs to cancer radio/chemotherapy resistance remains a challenge, requiring further clarification. In this review, we have presented the latest available information on the ways and means of regulating ferroptosis by ncRNAs. Moreover, we have provided important insights about targeting ncRNAs implicated in ferroptosis with the hope of opening up new horizons for overcoming cancer treatment modalities. Though a long path awaits until we make this ambitious dream come true, recent progress in gene therapy, including gene-editing technology will aid us to be optimistic that ncRNAs-based ferroptosis targeting would soon be on stream as a novel therapeutic strategy for treating cancer.

尽管癌症治疗近期取得了进展，但癌症的化疗耐药性与放疗耐药性一同凸显，这是一个亟待深入细致研究的重大挑战。不久前，据报道癌细胞已被证实对铁死亡这种新发现的程序性细胞死亡形式（RCD）具有抵抗性，这一现象十分显著，足以引起学者们将铁死亡作为一种潜在治疗策略的关注。然而，我们对于癌细胞获得对铁死亡免疫的潜在分子机制的了解仍处于起步阶段。最近，非编码RNA（ncRNAs）包括环状RNA（circRNAs）、微小RNA（miRNAs）和长链非编码RNA（lncRNAs）在铁死亡中的作用已被揭示。尽管如此，准确解释ncRNAs对癌症放/化疗耐药性的作用背后的分子机制仍然是一个挑战，需要进一步阐明。在这篇综述中，我们介绍了关于ncRNAs调节铁死亡的方式方法的最新可用信息。此外，我们提供了关于靶向与铁死亡相关的ncRNAs的重要见解，希望为克服癌症治疗模式开辟新的视野。尽管在实现这一雄心勃勃的梦想之前还有很长的路要走，但基因治疗（包括基因编辑技术）的近期进展使我们乐观地认为，基于ncRNAs的铁死亡靶向治疗将很快作为一种治疗癌症的新型治疗策略投入使用。