MEIS1 regulated proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension

Yao, Mao-Zhong; Ge, Xinlan; Liu, Ting; Liu, Hong; Chen, Yu; Zhang, Zheng; Hu, Chang-Ping

doi:10.1016/j.lfs.2020.117822

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…Meis1 can cooperate with Hoxb13 to regulate the maturation and cell cycle of cardiomyocytes ( Nguyen et al, 2020 ). Under hypoxia, knocking down MEIS1 induces PASMC proliferation and migration ( Locatelli et al, 2020 ; Yao et al, 2020 ). HDAC1 reduces pathological vascular calcification both in vivo and in vitro ( Zhou R. M. et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction

et al. 2021

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BackgroundAcute myocardial infarction (AMI), a common complex disease caused by an interaction between genetic and environmental factors, is a serious type of coronary artery disease and is also a leading cause of death worldwide. Autophagy-related 16-like 1 (ATG16L1) is a key regulatory factor of autophagy and plays an important role in induced autophagy. In the cardiovascular system, autophagy is essential to preserve the homeostasis and function of the heart and blood vessels. No studies have hitherto examined the association between AMI and ATG16L1 gene promoter.MethodsWe conducted a case-control study, using polymerase chain reaction and sequencing techniques, dual luciferase reporter assay, and electrophoretic mobility shift assay, to analyze genetic and functional variation in the ATG16L1 gene promoter between AMI and controls. A variety of statistical analyses were used to analyze the allele and genotype frequencies and the relationship between single-nucleotide polymorphisms (SNPs) and AMI.ResultsIn all, 10 SNPs and two DNA-sequence variants (DSVs) were identified in 688 subjects, and three ATG16L1 gene promoter mutations [g.233250693 T > C (rs185213911), g.233250946 G > A (rs568956599), g.233251133 C > G (rs1301744254)] that were identified in AMI patients significantly altered the transcriptional activity of ATG16L1 gene promoter in HEH2, HEK-293, and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assays indicated that the SNPs affected the binding of transcription factors (P < 0.01).ConclusionATG16L1 gene promoter mutations in AMI patients may affect the binding of transcription factors and change the transcriptional activity of the ATG16L1 gene, changing the level of autophagy and contributing to the occurrence and development of AMI as rare and low-frequency risk factors.

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Section: Resultsmentioning

confidence: 99%

Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction

et al. 2021

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“…In the HPH rat model, mRNA levels of Tc1 and Trps1 were increased in adult rats after postnatal hypoxia. In another study, hypoxia was shown to downregulate the expression of MEIS1 in pulmonary arteries which led to increased proliferation and migration of PASMCs [ 139 ]. This downregulation of MEIS1 was dependent on METTL14 m6A writer, which was highly upregulated under hypoxic conditions [ 139 ].…”

Section: Epitranscriptomic Modifications In Other Pulmonary Diseasesmentioning

confidence: 99%

“…In another study, hypoxia was shown to downregulate the expression of MEIS1 in pulmonary arteries which led to increased proliferation and migration of PASMCs [ 139 ]. This downregulation of MEIS1 was dependent on METTL14 m6A writer, which was highly upregulated under hypoxic conditions [ 139 ]. Additionally, PASMC proliferation can also occur via the STAT3 pathway [ 140 ].…”

Section: Epitranscriptomic Modifications In Other Pulmonary Diseasesmentioning

confidence: 99%

RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases

Teng

Liang

Yarmishyn

et al. 2021

IJMS

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Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

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“…The SETD2 catalyzes the trimethylation of lysine 36 on histone 3 (H3K36me3) and is involved in hypoxic PAH ( Yao et al, 2020 ). The expression of SETD2 and m6A writer METTL14 increase in hypoxia induced PASMCs of PAH mice.…”

Section: Roles Of Rna Methylations In Cvdsmentioning

confidence: 99%

RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

et al. 2021

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the world. Despite considerable progress in the diagnosis, treatment and prognosis of CVDs, new diagnostic biomarkers and new therapeutic measures are urgently needed to reduce the mortality of CVDs and improve the therapeutic effect. RNA methylations regulate almost all aspects of RNA processing, such as RNA nuclear export, translation, splicing and non-coding RNA processing. In view of the importance of RNA methylations in the pathogenesis of diseases, this work reviews the molecular structures, biological functions of five kinds of RNA methylations (m6A, m5C, m1a, m6am and m7G) and their effects on CVDs, including pulmonary hypertension, hypertension, vascular calcification, cardiac hypertrophy, heart failure. In CVDs, m6A “writers” catalyze the installation of m6A on RNAs, while “erasers” remove these modifications. Finally, the “readers” of m6A further influence the mRNA splicing, nuclear export, translation and degradation. M5C, m1A, m6Am and m7G are new types of RNA methylations, their roles in CVDs need to be further explored. RNA methylations have become a new research hotspot and the roles in CVDs is gradually emerging, the review of the molecular characteristics, biological functions and effects of RNA methylation on CVDs will contribute to the elucidation of the pathological mechanisms of CVDs and the discovery of new diagnostic markers and therapeutic targets of CVDs.

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MEIS1 regulated proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension

Cited by 11 publications

References 31 publications

Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction

Genetic Variants and Functional Analyses of the ATG16L1 Gene Promoter in Acute Myocardial Infarction

RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases

RNA Methylations in Cardiovascular Diseases, Molecular Structure, Biological Functions and Regulatory Roles in Cardiovascular Diseases

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