m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma

Zhang, Qijie; Luan, Jiaochen; Song, Lebin; Cong, Rong; Ji, Chen-jian; Zhou, Xiang; Xia, Jun; Song, Ninghong

doi:10.1016/j.yexcr.2020.112015

Cited by 28 publications

(22 citation statements)

References 30 publications

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“…Tomato MBD5 interacts with UV-damaged DNA binding protein-1 (31). m6A RNA methylation regulators correlate with malignant progression (32) and METTL3 inhibits PI3K/Akt signaling pathway (33). At present, there are few reports about miR-155 regulating the m6A methylation modi cation of DNMT1 mRNA through METTL3, and its speci c mechanism still needs to be further clari ed.…”

Section: Discussionmentioning

confidence: 99%

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Lu¹,

Chen²,

Xin³

et al. 2020

Preprint

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Background: miR-155 is a widely reported carcinogenic miRNA, with up-regulated expression in a variety of human cancers. Methods: Liver cancer stem cells were isolated from Huh7 cells; gene infection, RT-PCR, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: we demonstrate that miR-155 inhibits the expression of MBD5 and METTL3 , reducing the expression of DNMT1. In particular, miR155 inhibits the interaction between MBD5 and DNMT1, thereby inhibiting the binding capacity among MBD5, DNMT1 and IGFII (H19 ICR, IGFII DMR, IGFII Enhancer) DNA, inhibiting IGFII DNA methylation modification. Importantly, miR-155 promotes the formation of DNA loops in the IGFII DNA region (H19 ICR-IGFII Enhancer, IGFII DMR-IGFII Enhancer). Therefore, miR155 promotes the binding ability of H19-pre miR675 to histone methyltransferases SUV39h2 dependent on the H19 ICR-IGFII enhancer DNA loop and enhances the methylation modification of histone H3 on the ninth lysine . Then, the binding ability of RNA polII to P300 was enhanced by the formation of H3K9me2-RNA polII-P300 complex. Furthermore, miR155 promotes the binding ability of the RNA PolII-P300 complex to the IGFII promoter dependent on the IGFII DMR-IGFII enhancer DNA loop and promotes the expression of IGFII. Further research shows that miR155 promotes the binding of IGFII to stemness factors and the loading of stemness factors into the promoter region of HGF, which promotes the expression of hepatocyte growth factor HGF. In particular, miR155 promotes the expression of albumin gene (ALB) via HGF-c-MET, and then promotes the Sirt1 expression through ALB. Strikingly, miR155 promotes the autophagy dependent on acetylase Sirt1,including that miR155 promotes LC3 activation dependent on acetylase sirt1 and enhances binding capacity of LC3 to TP53INP2 / DOR, ATG4, ATG3 and ATG7, and the binding ability of the interaction between ATG5, ATG12, ATG6L1, ATG9. More meaningfully, miR155 enhances the ability of H-Ras to bind to the autophagosomes Beclin1, vps34, vps5, Uvrage, bif1, Lamp1, Lamp2, Lamp3, Rubicon, Rab24 dependent on autophagy, thereby enhancing the expression of H-Ras. Furthermore, miR155 enhances the expression of pRaf1, pMEK1 / 2, pERK1 / 2, pElK, pJak, Jun, pAKT, pmTOR, P70S6K, 4E-BP1, SGK1, C-myc dependent on H-Ras.Finally, miR-155 promotes the malignant growth of human liver cancer stem cells mediated by H-Ras.Conclusions: these results provide a valuable theoretical basis for therapeutic targets of liver cancer based on miR-155.

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Section: Discussionmentioning

confidence: 99%

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Lu¹,

Chen²,

Xin³

et al. 2020

Preprint

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“…Four genes were identified related with patients' survival (P < 0.1), and were further selected for functional analysis and potential risk signature using least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. Eventually, three genes and their coefficients were identified, selecting the best penalty parameter λ associated with the smallest 10-fold cross validation within TCGA database 21 . A risk score was calculated for the prognosis of each patient in TCGA dataset using the formula: risk score = ΣCoefi∗xi.…”

Section: Methodsmentioning

confidence: 99%

Data mining analysis of the prognostic impact of N⁶-methyladenosine regulators in patients with endometrial adenocarcinoma

Zhai¹,

Li²,

Liu³

et al. 2021

J. Cancer

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We reanalyzed the expression of 16 acknowledged N 6 -methyladenosine (m 6 A) RNA regulators in 406 endometrial adenocarcinoma patients and 19 controls using The Cancer Genome Atlas (TCGA) dataset, and further verified our results using Gene Expression Omnibus (GEO) dataset and real-time quantitative polymerase chain reaction. Thirteen m 6 A RNA methylation regulators were differentially expressed between patients with endometrial adenocarcinoma and controls. FTO, RBM15, and YTHDF1, were identified as independent prognostic markers and closely associated with International Federation of Gynecology and Obstetrics grade in endometrial cancer patients. GEO dataset also verified the differential expression of FTO and RBM15 between patients with endometrial adenocarcinoma and hyperplasia. Functional enrichment and ingenuity pathway analysis network suggested that FTO and RBM15 contributed to the survival of patients with endometrial adenocarcinoma via the regulation of connective tissue development, catabolic process, RNA stability, oxidative demethylation, temperature homeostasis, and energy metabolism through IGF1, IRS1, RBM24, LARP1, and CBFA2T3. The decreased FTO expression and increased RBM15 expression in endometrial adenocarcinoma from our validation cohort was consistent with in silico analysis using TCGA and GEO datasets. In conclusion, m 6 A methylation regulators, especially FTO, RBM15, and YTHDF1, are critical in the progression and prognosis of endometrial adenocarcinoma.

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“…According to different RNA epigenetics, immune status and biological process, three different subtypes of sepsis have been identified ( Salomão et al, 2019 ). In view of the characteristics of m6A methylation regulatory genes, m6A methylation may be the main reason for the heterogeneity of sepsis ( Zhang et al, 2020c ).…”

Section: Biological Functions Of Rna Methylationsmentioning

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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m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma

Cited by 28 publications

References 30 publications

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Data mining analysis of the prognostic impact of N⁶-methyladenosine regulators in patients with endometrial adenocarcinoma

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

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m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma

Cited by 28 publications

References 30 publications

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Data mining analysis of the prognostic impact of N6-methyladenosine regulators in patients with endometrial adenocarcinoma

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

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Data mining analysis of the prognostic impact of N⁶-methyladenosine regulators in patients with endometrial adenocarcinoma