STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma

Redox Biology, Journal Year: 2023, Volume and Issue: 60, P. 102626 - 102626

Published: Feb. 2, 2023

Radioresistance is the major reason for failure of radiotherapy in esophageal squamous cell carcinoma (ESCC). Previous evidence indicated that stanniocalcin 2 (STC2) participates various biological processes malignant tumors. However, researches on its effect radioresistance cancers are limited. In this study, STC2 was screened out by RNA-sequencing and bioinformatics analyses as a potential prognosis predictor ESCC radiosensitivity then determined to facilitate radioresistance. We found expression increased tissues compared adjacent normal tissues, higher level associated with poor prognosis. Also, mRNA protein levels were radioresistant cells than their parental cells. Further investigation revealed could interact methyltransferase 5 (PRMT5) activate PRMT5, thus leading symmetric dimethylation histone H4 Arg 3 (H4R3me2s). Mechanistically, can promote DDR through homologous recombination non-homologous end joining pathways activating PRMT5. Meanwhile, participate SLC7A11-mediated ferroptosis PRMT5-dependent manner. Finally, these results validated vivo experiments. These findings uncovered might be an attractive therapeutic target overcome

Language: Английский

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The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer

International Journal of Cancer, Journal Year: 2023, Volume and Issue: 153(5), P. 918 - 931

Published: Feb. 27, 2023

Abstract Oncogene‐induced hyper‐proliferation in cancer cells is accompanied by the onset of different stresses, including DNA‐replication stress, metabolic stress and oxidative stress. Excessive accumulation reactive oxygen species (ROS) plays a pivotal contradictory role tumor progression. ROS dictates multitude cell signaling pathways to facilitate malignant transformation cells. In meantime, burden mandates reinforcing antioxidant capacity mitigate detrimental damages. The addiction increased iron demands also impinges on sensitivity ferroptosis. Targeting redox homeostasis ferroptosis overcome drug resistance treatment has become an attractive research topic. However, roles oncogenic regulation have not been comprehensively discussed. this review, we summarize current knowledge regarding interplay between context biology. We emphasize implication regulation. provide overview strategies targeting treatment.

Language: Английский

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Aloe-emodin alleviates doxorubicin-induced cardiotoxicity via inhibition of ferroptosis

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 206, P. 13 - 21

Published: June 25, 2023

Language: Английский

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Depletion of SOD2 enhances nasopharyngeal carcinoma cell radiosensitivity via ferroptosis induction modulated by DHODH inhibition

BMC Cancer, Journal Year: 2023, Volume and Issue: 23(1)

Published: Feb. 3, 2023

Recurrence due to the development of radioresistance remains a major challenge in clinical management nasopharyngeal carcinoma. The objective this study was increase sensitivity carcinoma cells ionizing radiation by enhancing oxidative stress and ferroptosis caused disrupting mitochondrial anti-oxidant enzyme system.Oxidative cell model constructed SOD2 knockdown using shRNA. expression activity DHODH suppressed siRNA brequinar depleted cells. Protein levels were determined western blotting assessed C11 BODIPY malondialdehyde assay. Cell viability evaluated CCK-8 assay while radiotoxicity colony formation Cellular ATP level kits, ROS DCFD DHE, oxygen consumption seahorse Data analyzed two-tailed independent t-test.Radiation upregulated depletion increased cellular O2.-, malondialdehyde, fluorescence intensity oxidized BODIPY. It also resulted damage. Its decreased both under non-ionizing conditions. inhibitor, deferoxamine, rescued BODIPY, O2.- level, ATP, following inhibition cells.Inducing sensitized via induction. This found be dependent on activity. suggests that inhibitors should used with caution during radiotherapy patients.

Language: Английский

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Butyrate dictates ferroptosis sensitivity through FFAR2-mTOR signaling

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 25, 2023

Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce apoptosis autophagy. However, it remains largely unclear whether can regulate cell ferroptosis, the mechanism by which has not been studied. this study, we found RAS-selective lethal compound 3 (RSL3)- erastin-induced ferroptosis were enhanced sodium (NaB). With regard underlying mechanism, our results showed NaB promoted inducing lipid ROS production via downregulating expression of solute carrier family 7 member 11 (SLC7A11) glutathione peroxidase 4 (GPX4). Moreover, FFAR2-AKT-NRF2 axis FFAR2-mTORC1 accounts for NaB-mediated downregulation SLC7A11 GPX4, respectively, a cAMP-PKA-dependent manner. Functionally, inhibit tumor growth inhibitory effect could be eliminated administrating MHY1485 (mTORC1 activator) Ferr-1 (ferroptosis inhibitor). Altogether, vivo suggest treatment correlated mTOR-dependent consequent through xenografts colitis-associated colorectal tumorigenesis, implicating potential clinical applications future cancer treatments. Based on all these findings, have proposed regulatory inhibits mTOR pathway control tumorigenesis.

Language: Английский

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