o8G-modified circPLCE1 inhibits lung cancer progression via chaperone-mediated autophagy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 17, 2025

Lung cancer poses a serious threat to human health, but its molecular mechanisms remain unclear. Circular RNAs (circRNAs) are closely associated with tumour progression, and the important role of 8-oxoguanine (o8G) modification in regulating fate RNA has been gradually revealed. However, o8G circRNAs not reported. We identified circPLCE1, which is significantly downregulated lung cancer, further investigated circPLCE1 related mechanism progression. differentially expressed by high-throughput sequencing then conducted methylated immunoprecipitation (MeRIP), immunofluorescence (IF) analysis, crosslinking (CLIP) actinomycin D (ActD) assays explore modification. The biological functions vivo vitro were clarified via establishing silencing/overexpression system. Tagged affinity purification (TRAP), Immunoprecipitation (RIP) coimmunoprecipitation (Co-IP) assays, pSIN-PAmCherry-KFERQ-NE reporter gene used elucidate inhibits This study revealed that reactive oxygen species (ROS) can induce AUF1 mediate decrease stability. found inhibited progression expression was stage prognosis. elucidated: targets HSC70 protein, increases ubiquitination level, regulates ATG5-dependent macroautophagy chaperone-mediated autophagy (CMA) pathway, ultimately o8G-modified through CMA inhibit alter cell fate. provides only new theoretical basis for elucidating also potential treatment. ROS modification, specifically recognizes thereby decreases activity, promotes altering cells inhibiting

Language: Английский

---

Mapping the future of oxidative RNA damage in neurodegeneration: Rethinking the status quo with new tools

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(46)

Published: Nov. 4, 2024

Over two decades ago, increased levels of RNA oxidation were reported in postmortem patients with ALS, Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Interestingly, not all cell types transcripts equally oxidized. Furthermore, it was shown that is an early phenomenon, altogether indicating oxidative damage could be a driver, consequence, disease. Despite these exciting observations, the field appears to have stagnated since then. We argue this consequence shortcomings technologies model diseases, limiting our understanding which are being oxidized, RNA-binding proteins interacting RNAs, what their implications processing, as result, potential role disease onset progression. Here, we discuss limits previous propose ways by advancements iPSC-derived modeling, proteomics, sequencing can combined leveraged answer new decades-old questions.

Language: Английский

---

Dysregulation of Labile Iron Predisposes Chemotherapy Resistant Cancer Cells to Ferroptosis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4193 - 4193

Published: April 28, 2025

Despite centuries of research, metastatic cancer remains incurable due to resistance all conventional therapeutics. Alternative strategies leveraging non-proliferative vulnerabilities in are required overcome recurrence. Ferroptosis is an iron dependent cell death pathway that has shown promising pre-clinical activity several contexts therapeutic resistant cancer. However, ferroptosis sensitivity highly variable across tissue types and states, posing a challenge for clinical translation. We describe convergent phenotype induced by chemotherapy where cells surviving have dysregulated homeostasis, regardless initial type or used. Elevated labile levels counteracted NRF2 signaling, yet the resulting antioxidant programs do not alleviate burden. Selectively inhibiting GPX4 leads uniform susceptibility cells, highlighting common reliance on lipid peroxidation defenses. Cellular dysregulation vulnerability chemoresistant can be leveraged triggering ferroptosis.

Language: Английский

---

RNA–DNA Differences: Mechanisms, Oxidative Stress, Transcriptional Fidelity, and Health Implications

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 544 - 544

Published: April 30, 2025

RNA–DNA differences (RDDs) challenge the traditional view of RNA as a faithful copy DNA, arising through editing, transcriptional errors, and oxidative damage. Reactive oxygen species (ROS) play central role, inducing lesions like 8-oxo-guanine that compromise transcription translation, leading to dysfunctional proteins. This review explores biochemical basis RDDs, their exacerbation under stress, dual roles in cellular adaptation disease. RDDs contribute genomic instability are implicated cancers, neurodegenerative disorders, autoimmune diseases, while also driving phenotypic diversity. Drawing on terrestrial spaceflight studies, we highlight intersection RDD formation, dysfunction, proposing innovative mitigation approaches. Advancements detection quantification, along with ROS management therapies, offer new avenues restore homeostasis promote resilience. By positioning hallmark entropy, this underscores limits biological adaptation. Furthermore, prevalence guanine-rich codons antioxidant genes increases susceptibility ROS-induced lesions, linking redox instability, constrained These insights have profound implications for understanding aging, disease progression, adaptive mechanisms both space environments.

Language: Английский

---

Unlocking the potential of extracellular vesicle circRNAs in breast cancer: From molecular mechanisms to therapeutic horizons

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117480 - 117480

Published: Oct. 1, 2024

Language: Английский

---

o⁸G‐miR‐6513‐5p/BCL2L13 Axis Regulates Mitophagy during Oxidative Stress in the Human Saphenous Vein Endothelial Cells

Advanced Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 22, 2024

Venous graft decay (VGD) occurs in coronary artery bypass grafting (CABG), and ischemia-reperfusion oxidative stress injury during the operation is involved VGD. To explore cellular phenotypic changes this process, a stable model of human saphenous vein endothelial cells (HSVECs) constructed. Through proteomics cell experiments, it found that expression BCL2L13 upregulated HSVECs, regulated mitophagy through receptor-mediated interaction with LC3 plays role protection. During stress, intracellular o

Language: Английский

---