The Regulation of Ferroptosis by Noncoding RNAs

Abstract

As a novel form of regulated cell death, ferroptosis is characterized by intracellular iron and lipid peroxide accumulation, which is different from other regulated cell death forms morphologically, biochemically, and immunologically. Ferroptosis is regulated by iron metabolism, lipid metabolism, and antioxidant defense systems as well as various transcription factors and related signal pathways. Emerging evidence has highlighted that ferroptosis is associated with many physiological and pathological processes, including cancer, neurodegeneration diseases, cardiovascular diseases, and ischemia/reperfusion injury. Noncoding RNAs are a group of functional RNA molecules that are not translated into proteins, which can regulate gene expression in various manners. An increasing number of studies have shown that noncoding RNAs, especially miRNAs, lncRNAs, and circRNAs, can interfere with the progression of ferroptosis by modulating ferroptosis-related genes or proteins directly or indirectly. In this review, we summarize the basic mechanisms and regulations of ferroptosis and focus on the recent studies on the mechanism for different types of ncRNAs to regulate ferroptosis in different physiological and pathological conditions, which will deepen our understanding of ferroptosis regulation by noncoding RNAs and provide new insights into employing noncoding RNAs in ferroptosis-associated therapeutic strategies.

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

“…The intracellular antioxidant pathway resists the onset of ferroptosis by neutralizing lipid peroxides and is a critical ferroptosis defense system in the body. 33 Inhibiting antioxidant pathways disrupts ferroptosis defenses, leading to the induction of ferroptosis. Described below are a few of the major pathways involved in the induction of ferroptosis.…”

The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside

“…LncRNAs modulate ferroptosis-related pathways, leading to ferroptotic cell death [ 151 ]. LncRNA-based therapies have the potential for personalized cancer treatment due to tumor heterogeneity, and they may ultimately offer greater specificities than traditional ferroptosis-inducing agents.…”

Ferroptosis in health and disease

“…Non-coding RNAs have been shown to affect ferroptosis as well. Several miRNAs bind to the mRNAs of Gpx4 , SLC7A11 , and other ferroptosis-related proteins [ 297 ] leading to their degradation and thereby enhanced or impaired ferroptosis, respectively. Moreover, ncRNAs affect ferroptosis by targeting proteins responsible for lipid, redox, and iron homeostasis [ 297 ].…”

“…Several miRNAs bind to the mRNAs of Gpx4 , SLC7A11 , and other ferroptosis-related proteins [ 297 ] leading to their degradation and thereby enhanced or impaired ferroptosis, respectively. Moreover, ncRNAs affect ferroptosis by targeting proteins responsible for lipid, redox, and iron homeostasis [ 297 ]. Several long non-coding RNAs are associated with regulation of ferroptosis and specific diseases making them potential prognistic tools, such as the 36 lncRNAs that were linked to ferreoptosis as well as progression of bladder cancer [ 298 ].…”