m6A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension

Liu, Pengfei; Zhang, Aikai; Ding, Zheng; Dai, Dongpu; Liu, Shao‐Fei; Xu, Jingjing; Cheng, Zhe; Zhao, Song; Zhao, Xiaoyan; Dong, Jianzeng

doi:10.1165/rcmb.2021-0429oc

Cited by 16 publications

(12 citation statements)

References 35 publications

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“…Hence, understanding the molecular mechanisms behind NSCLC is crucial, especially in the pathogenesis of chemotherapy resistance. A number of studies have implicated m6A modification in diseases such as acute myeloid leukemia ( 14 ), hepatocellular carcinoma ( 15 ), type 2 diabetes ( 16 ), rheumatoid arthritis ( 17 ), and pulmonary hypertension ( 18 ). Recently, further studies have reported on m6A modification related protein’s biological function in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

YTHDC2-mediated m6A mRNA modification of Id3 suppresses cisplatin resistance in non-small cell lung cancer

Wang¹,

Hu²,

Li³

et al. 2023

J Thorac Dis

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Background: The methylation of adenosines at the N6 position (N6-methyladenosine; m6A) is one of the most conserved internal RNA modifications. m6A can modulate the expression of oncogenes or tumor suppressor genes, as well as m6A levels and the expression and activity of m6A enzymes, thus influencing tumor progression and therapeutic response. This study investigates the role of YTHDC2-mediated m6A messenger RNA (mRNA) modification of Id3 in controlling cisplatin resistance in non-small cell lung cancer (NSCLC). Methods:The expression of the m6A reader protein YTHDC2 was detected in an NSCLC cisplatinresistant cell line (A549/DDP) using real-time fluorescence quantitative polymerase chain reaction (qPCR).YTHDC2 overexpression plasmids were constructed and transfected into A549/DDP and A549 cells respectively. We performed qPCR and western blot (WB) to detect changes in YTHDC2 and Id3 expression, and the effects of YTHDC2 overexpression on proliferation, apoptosis, invasion, and migration of drugresistant cells were assessed by cell counting kit-8 (CCK-8), flow cytometry, and transwell and scratch assays.The m6A modification of Id3 by YTHDC2 was clarified by m6A-immunoprecipitation-PCR (m6A-IP-PCR) assay. Results:The CLIPdb online database predicted that YTHDC2 might bind to Id3. The results of qPCR showed that YTHDC2 was downregulated in the NSCLC cisplatin-resistant cell line A549/DDP compared to the cisplatin-sensitive cell line A549. Overexpression of YTHDC2 increased the expression of Id3, and the methylation inhibitor 3-deazaadenosine abrogated the regulatory effect of YTHDC2 on Id3. YTHDC2 overexpression significantly inhibited A549/DDP cell proliferation, migration, and invasion, and promoted apoptosis by synergistically promoting the effects of Id3. m6A-IP-PCR analysis revealed that YTHDC2 could inhibit the m6A level of Id3 mRNA.Conclusions: To regulate the activity of Id3, YTHDC2 requires modifications to m6A, which ultimately inhibit cisplatin resistance in NSCLC.

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Section: Discussionmentioning

confidence: 99%

YTHDC2-mediated m6A mRNA modification of Id3 suppresses cisplatin resistance in non-small cell lung cancer

Wang¹,

Hu²,

Li³

et al. 2023

J Thorac Dis

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“…no. S8442; MilliporeSigma) (17). Briefly, 8-week-old male C57BL/6JGpt mice (weight, 22-24 g) were housed with ad libitum access to food and water at 22˚C with 65% humidity and a 12-h light/dark cycle.…”

Section: Methodsmentioning

confidence: 99%

“…Hemodynamic measurements. Right ventricular systolic pressure (RVSP) was measured as previously described (17). Before measurement, mice were intraperitoneally anesthetized with 45 mg/kg pentobarbital sodium.…”

Section: Methodsmentioning

confidence: 99%

Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice

Zheng

Yan

et al. 2023

Int J Mol Med

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“…In another study, m6A-modified GRAP mRNA was upregulated in PAH lung samples, cHx/Su-induced mouse models, and hypoxia-stimulated HPASMCs, while METTL14 and m6A-binding proteins like YTHDF2, were significantly increased in PAH. Furthermore, GRAP expression was consistently and negatively correlated with METTL14 and YTHDF2 [18]. All the above studies have strived to understand and highlight the importance of RNA epigenetics in PAH.…”

Section: M6a Rna Methylationmentioning

confidence: 99%

N6-Methyladenosine Modifications in Pulmonary Hypertension

Xia,

Zhang,

Huang

et al. 2023

Pharmacology

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Background: The most prevalent kind of RNA methylation modification existing in eukaryotes is N6-methyladenosine (m6A), which is a reversible type of posttranscriptional modification. Summary: Many studies have reported that m6A participates in cell differentiation, self-renewal, invasion, and apoptosis by modifying protein synthesis. Furthermore, m6A modification is also involved in disease progression and pulmonary vascular remodeling in pulmonary hypertension. However, very few researchers have investigated the effect of m6A modifications on pulmonary hypertension. Key Messages: Here, we have reviewed the latest research advances in the field of m6A RNA methylation in pulmonary hypertension and explored its regulatory role in pulmonary hypertension development and progression.

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m⁶A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension

Cited by 16 publications

References 35 publications

YTHDC2-mediated m6A mRNA modification of Id3 suppresses cisplatin resistance in non-small cell lung cancer

YTHDC2-mediated m6A mRNA modification of Id3 suppresses cisplatin resistance in non-small cell lung cancer

Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice

N6-Methyladenosine Modifications in Pulmonary Hypertension

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