METTL14 alleviates the development of osteoporosis in ovariectomized mice by upregulating m6A level of SIRT1 mRNA

Wang, Changsheng; Chen, Rongsheng; Zhu, Xitian; Zhang, Xiaobo; Lian, Nancheng

doi:10.1016/j.bone.2022.116652

Cited by 11 publications

(3 citation statements)

References 39 publications

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“…[40] A study on spinal cord injury associated downregulated USP7 and upregulated HMOX-1 with improved motor function recovery and ferroptosis prevention. [41] These findings collectively emphasize the critical regulatory influence of USP7 in ferroptosis across various pathological conditions, presenting potential therapeutic avenues. However, the specific role of USP7 in regulating ferroptosis in GC requires further exploration.…”

Section: Discussionmentioning

confidence: 78%

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Guan,

Wang,

et al. 2024

Advanced Science

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Gastric cancer (GC) presents a formidable global health challenge, and conventional therapies face efficacy limitations. Ubiquitin‐specific protease 7 (USP7) plays pivotal roles in GC development, immune response, and chemo‐resistance, making it a promising target. Various USP7 inhibitors have shown selectivity and efficacy in preclinical studies. However, the mechanistic role of USP7 has not been fully elucidated, and currently, no USP7 inhibitors have been approved for clinical use. In this study, DHPO is identified as a potent USP7 inhibitor for GC treatment through in silico screening. DHPO demonstrates significant anti‐tumor activity in vitro, inhibiting cell viability and clonogenic ability, and preventing tumor migration and invasion. In vivo studies using orthotopic gastric tumor mouse models validate DHPO's efficacy in suppressing tumor growth and metastasis without significant toxicity. Mechanistically, DHPO inhibition triggers ferroptosis, evidenced by mitochondrial alterations, lipid Reactive Oxygen Species (ROS), Malondialdehyde (MDA) accumulation, and iron overload. Further investigations unveil USP7's regulation of Stearoyl‐CoA Desaturase (SCD) through deubiquitination, linking USP7 inhibition to SCD degradation and ferroptosis induction. Overall, this study identifies USP7 as a key player in ferroptosis of GC, elucidates DHPO's inhibitory mechanisms, and highlights its potential for GC treatment by inducing ferroptosis through SCD regulation.

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Section: Discussionmentioning

confidence: 78%

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Guan,

Wang,

et al. 2024

Advanced Science

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“…METTL3 and METTL14 can be novel targets for OP treatment due to diverse regulatory roles on osteoblasts, osteoclasts and BMSCs. For example, METTL14 overexpression suppressed osteoclast differentiation via enhancing GPX4 mRNA stability [ 133 ], and METTL14 overexpression increased SIRT1 mRNA expression to promoted osteoblast differentiation [ 134 ], and METTL14 overexpression was found to promote the osteogenic differentiation ability of BMSCs [ 137 ]. Although diverse regulatory roles of METTL3, METTL14 and FTO show the novel targets for OP treatment, there is lack of research to develop therapeutic strategies targeting METTL3 and METTL14.…”

Section: M6a and Skeletal System Diseasementioning

confidence: 99%

“…Deng and colleagues found that METTL14 was downregulated in postmenopausal osteoporotic women and overexpression of METTL14 can suppress osteoclast formation to ameliorate osteoporosis by stabilizing GPX4 [133]. Moreover, Wang et al illustrated that METTL14 could alleviate OP via upregulating m6A level of SIRT1 mRNA [134]. Meanwhile, FTO and WTAP participate in alleviating OP through negatively regulation of osteoclast differentiation [120,140] YTHDF2 and TRAF6 mRNA nuclear export [148].…”

Section: M6a and Osteoporosismentioning

confidence: 99%

Recent advances of m6A methylation in skeletal system disease

Liang,

Yi,

Liu

et al. 2024

J Transl Med

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Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.

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KLF7 reverses ox-LDL-induced ferroptosis in HMEC-1 cells through transcriptionally activating ALKBH5 to inhibit the m6A modification of ACSL4

Xiong,

Luo,

Xie

et al. 2024

Cytotechnology

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METTL14 alleviates the development of osteoporosis in ovariectomized mice by upregulating m6A level of SIRT1 mRNA

Cited by 11 publications

References 39 publications

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Recent advances of m6A methylation in skeletal system disease

KLF7 reverses ox-LDL-induced ferroptosis in HMEC-1 cells through transcriptionally activating ALKBH5 to inhibit the m6A modification of ACSL4

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