Non-coding RNAs and ferroptosis: potential implications for cancer therapy

Abstract

Ferroptosis is a recently defined form of regulated cell death, which is biochemically and morphologically distinct from traditional forms of programmed cell death such as apoptosis or necrosis. It is driven by iron, reactive oxygen species, and phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage and breakdown of membrane integrity. Numerous cellular signaling pathways and molecules are involved in the regulation of ferroptosis, including enzymes that control the cellular redox status. Alterations in the ferroptosis-regulating network can contribute to the development of various diseases, including cancer. Evidence suggests that ferroptosis is commonly suppressed in cancer cells, allowing them to survive and progress. However, cancer cells which are resistant to common chemotherapeutic drugs seem to be highly susceptible to ferroptosis inducers, highlighting the great potential of pharmacologic modulation of ferroptosis for cancer treatment. Non-coding RNAs (ncRNAs) are considered master regulators of various cellular processes, particularly in cancer where they have been implicated in all hallmarks of cancer. Recent work also demonstrated their involvement in the molecular control of ferroptosis. Hence, ncRNA-based therapeutics represent an exciting alternative to modulate ferroptosis for cancer therapy. This review summarizes the ncRNAs implicated in the regulation of ferroptosis in cancer and highlights their underlying molecular mechanisms in the light of potential therapeutic applications.

CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

“…Although many studies have discovered the detailed mechanism and critical signaling pathways of ferroptosis, the mechanism of ncRNAs, especially circRNAs, in the occurrence and progression of ferroptosis is still unclear [ 19 ]. Only a few studies have revealed the role of circRNAs in ferroptosis and GBM.…”

“…CircLMO1 suppresses cervical cancer growth and promotes cervical cancer cell ferroptosis through up-regulating ACSL4 expression [ 18 ]. However, as master regulators of various cellular processes [ 19 ], it is worth studying novel circRNAs regulate ferroptosis in GSCs.…”

Editorial: Implications of Ferroptosis-Related Genes to the Genetics of Cancer Development

“…LncRNAs are considered to be major regulators of various cellular processes, and their dysregulation is implicated in all features of cancer (Balihodzic et al, 2021). More and more evidence confirmed the importance of lncRNA in regulating ferroptosis (Balihodzic et al, 2022). LncRNAs can regulate the expression of GPX4 and induce lipid peroxidation of the cell membrane through sponge miRNAs, resulting in the ferroptosis of cancer cells (Zuo et al, 2022).…”

Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications

“…NcRNAs can regulate cancer progression outside the primary cancer cells via EV-mediated transfer to recipient cells [ 9 ]. EV-ncRNAs are master regulators of various cellular processes and play an important role during carcinogenesis [ 10 ]. Tumor cell-derived EV-ncRNAs influence epithelial-mesenchymal transition (EMT), cell proliferation, metastasis, angiogenesis, drug resistance, and inflammation [ 11 ].…”