RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment

Ruan, Fengkai; Zeng, Jie; Yin, Hanying; Jiang, Shengwei; Cao, Xisen; Zheng, Naying; Han, Changshun; Zhang, Chuchu; Zuo, Zhenghong; He, Chengyong

doi:10.1002/smtd.202001045

Cited by 39 publications

(31 citation statements)

References 54 publications

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“…A large number of previous studies have found that m 6 A methylation levels can regulate genes involved in the regulation of ferroptosis. Studies have found that m 6 A modification enhances ferroptosis in stellate cells by stabilizing BECN1mRNA to trigger autophagy activation [ 16 ]. Other studies have found that METTL3-mediated m 6 A methylation can stabilize SLC7A11mRNA and accelerate translation, thereby inhibiting ferroptosis and accelerating the proliferation of lung cancer cells [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

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mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth

Wang¹,

Yu²,

Wang³

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Regarding the imperfect mechanism of occurrence and development of prostate adenocarcinoma (PRAD), this study investigated mRNA-modified FUS/NRF2 signalling to inhibit ferroptosis and promote prostate adenocarcinoma growth. Methods. Bioinformatics analysis was used to obtain the expression of FUS and its mRNA modification in PRAD. The expression of FUS in prostate cells (CRPC) and the level of m6A methylation modification, ferroptosis (P53 and GPX4), apoptosis (Caspase3), ferroptosis (P53 and GPX4), and apoptosis (Caspase3) in CRPC after ferroptosis inducer Erastin, ferroptosis inhibitor, and FUS knockdown were detected. Autophagy (LC3B), oxidative stress (GSH and ROS), and expression of NRF2/HO-1 pathway are indicators. Results. FUS was highly expressed in PRAD and phenomenally reduced the survival rate of patients. After knocking down FUS, the level of m6A methylation was significantly reduced, and the expressions of ferroptosis markers P53 and GPX4 were phenomenally reduced, while the levels of apoptosis and autophagy markers Caspase3 and LC3B remained unchanged. Upregulated and NRF2/HO-1 pathway indicators were upregulated. It shows that m6A methylation modification is reduced when FUS is the low expression, inhibits the expression of P53 and GPX4, downregulates GSH, upregulates ROS, activates the NRF2/HO-1 pathway, and promotes ferroptosis to inhibit the occurrence of RPAD. Conclusions. The increase of m6A methylation modification can increase the expression of FUS, thereby promoting the expression of P53 and GPX4, upregulating GSH, downregulating ROS, inhibiting the NRF2/HO-1 pathway, inhibiting ferroptosis, and promoting the growth of PRAD.

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Section: Discussionmentioning

confidence: 99%

“…The modification methods of mRNA consist of N6-adenine (m 6 A), n1-adenine (m1A), pseudouracil, and 5′-cytosine methylation, of which m6A is the most common [ 10 , 16 ]. These modifications affect the splicing, expression, and translation of mRNA, etc.…”

Section: Introductionmentioning

confidence: 99%

mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth

Wang¹,

Yu²,

Wang³

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Furthermore, considering their easy inhalation ability, we used lung cells to further evaluate the bioimpacts of BPQDs and their correlation with m 6 A RNA modification. Surprisingly, the global m 6 A level was increased after BPQD exposure in lung cells, and after the protein expression of m 6 A-related proteins was examined, we further clarified the significant role of ALKBH5 in this event; the expression of “writers” and other “erasers” did not change, but ALKBH5 decreased with BPQD exposure [ 105 ]. Transcriptome and epitranscriptome data have provided evidence of the correlation between the abnormal elevation of total m 6 A levels and the aberrant expression of genes related to ferroptosis involving ER stress, iron homeostasis and iron homeostasis, which has also been verified by evidence of iron overload, lipid peroxidation, glutathione peroxidase 4 (GPX4) downregulation and glutathione (GSH) depletion in vitro.…”

Section: M 6 a Rna Modification Modulates The Bioi...mentioning

confidence: 99%

“…MPNPs improve anti-virus ability in VSV-infected macrophages. TiO 2 -NPs cause cardiac impairment by upregulating the total m 6 A level [ 104 , 105 , 106 , 107 , 108 , 109 , 110 ].…”

Section: Figurementioning

confidence: 99%

Nanoparticle-Induced m6A RNA Modification: Detection Methods, Mechanisms and Applications

et al. 2022

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With the increasing application of nanoparticles (NPs) in medical and consumer applications, it is necessary to ensure their safety. As m6A (N6-methyladenosine) RNA modification is one of the most prevalent RNA modifications involved in many diseases and essential biological processes, the relationship between nanoparticles and m6A RNA modification for the modulation of these events has attracted substantial research interest. However, there is limited knowledge regarding the relationship between nanoparticles and m6A RNA modification, but evidence is beginning to emerge. Therefore, a summary of these aspects from current research on nanoparticle-induced m6A RNA modification is timely and significant. In this review, we highlight the roles of m6A RNA modification in the bioimpacts of nanoparticles and thus elaborate on the mechanisms of nanoparticle-induced m6A RNA modification. We also summarize the dynamic regulation and biofunctions of m6A RNA modification. Moreover, we emphasize recent advances in the application perspective of nanoparticle-induced m6A RNA modification in medication and toxicity of nanoparticles to provide a potential method to facilitate the design of nanoparticles by deliberately tuning m6A RNA modification.

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“…Aberrant m 6 A as crucial drivers of multiple diseases (especially cancers) can provide an epitranscriptomic indicator of cellular responses and pathogenetic effects induced by nanomaterials, of which field remains largely unknown [ 40 – 43 ]. Although several omics-based approaches have been used to assess biological effects of nanomaterials, the epitranscriptomics has rarely been applied in the field of nanosafety evaluations so far [ 44 ]. Therefore, it is of great significance to investigate the nanomaterial-induced epitranscriptomics scenery.…”

Section: Introductionmentioning

confidence: 99%

RNA m6A Alterations Induced by Biomineralization Nanoparticles: A Proof-of-Concept Study of Epitranscriptomics for Nanotoxicity Evaluation

et al. 2022

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Although various strategies have been included in nanotoxicity evaluation, epitranscriptomics has rarely been integrated into this field. In this proof-of-concept study, N6-methyladenosine (m6A) changes of mRNA in HEK293T cells induced by three bovine serum albumin (BSA)-templated Au, CuS and Gd2O3 nanoparticles are systematically explored, and their possible biological mechanisms are preliminarily investigated. It has been found that all the three BSA-templated nanoparticles can reduce m6A levels, and the genes with reduced m6A are enriched for TGF-beta signaling, which is critical for cell proliferation, differentiation and apoptosis. Further results indicate that abnormal aggregation of m6A-related enzymes at least partly account for the nanoparticle-induced epitranscriptomic changes. These findings demonstrate that epitranscriptomics analysis can provide an unprecedented landscape of the biological effect induced by nanomaterials, which should be involved in the nanotoxicity evaluation to promote the potential clinical translation of nanomaterials.

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RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment

Cited by 39 publications

References 54 publications

mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth

mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth

Nanoparticle-Induced m6A RNA Modification: Detection Methods, Mechanisms and Applications

RNA m6A Alterations Induced by Biomineralization Nanoparticles: A Proof-of-Concept Study of Epitranscriptomics for Nanotoxicity Evaluation

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