Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers.
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Wang et al. as discussed by the authors characterized the variation in expression profile of RNA m6A regulators in 13 cancer types from The Cancer Genome Atlas (TCGA), revealing that METTL14, FTO, and ALKBH5 were downregulated in most cancer types, whereas YTHDF1 and IGF2BP3 were upregulated in 12 cancer types except for thyroid carcinoma (THCA).Abstract:
Background: N6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely “writers”, “erasers”, and “readers”. Increasing evidence showed that RNA m6A modification plays an essential role in cancer development and aberrant expression of m6A regulators can affect tumor progression and metastasis. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers. Results: Here we characterized the variation in expression profile of RNA m6A regulators in 13 cancer types from The Cancer Genome Atlas (TCGA), revealing that METTL14, FTO, and ALKBH5 were down-regulated in most cancer types, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis with clinical information further revealed that high expression of several m6A regulators was correlated with the poor prognosis of patients in different cancers. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 150 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators in pan-cancer. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer pathogenesis and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) act as tumor suppressors, suggesting their potential as prognostic biomarkers. To evaluate the potential clinical application for those regulatory pairs, we validated two key miRNA/mRNA pairs (hsa-mir-18a/EIF3A and hsa-mir-304/IGF2BP3) in KIRC patients and found that these two pairs could well evaluate the survival of patients. Conclusions: Our findings highlighted the importance of upstream molecules (miRNAs and DNA methylation) governing m6A regulators’ expression in pan-cancer, and identified several regulatory pairs informative for prognostic stratification, which provide new insights into molecular mechanisms of m6A modification in human cancers.read more
Citations
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N6-methyladenosine methyltransferases: functions, regulation, and clinical potential
TL;DR: In this article, the authors summarize the function of these m6A methyltransferases or complexes in regulating the key genes and pathways of cancer biology and highlight the progress in the use of m6As in mediating therapy resistance, including chemotherapy, targeted therapy, immunotherapy and radiotherapy.
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Functions, mechanisms, and therapeutic implications of METTL14 in human cancer
TL;DR: Zhang et al. as discussed by the authors systematically summarized the latest research progress on METTL14 as a new biomarker for cancer diagnosis and its biological function in human tumors and discuss its potential clinical application.
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N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors.
Lei Zhan,Junhui Zhang,Junhui Zhang,Suding Zhu,Xiaojing Liu,Jing Zhang,Wenyan Wang,Yijun Fan,Shiying Sun,Bing Wei,Yunxia Cao,Yunxia Cao +11 more
TL;DR: In this article, the role of m6A RNA modification in cold tumor formation and regulation is discussed, and the potential clinical implications and immunotherapeutic approaches of the modification in cancer patients are discussed.
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Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma.
Yinde Huang,Xin Li,Wenbin Chen,Yuzhen He,Song Wu,Xinyang Li,Bingchen Hou,Shiyue Wang,Yuchen He,Han Jiang,Yu Lun,Jian Zhang +11 more
TL;DR: In this article, consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related long non-coding RNAs.
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Construction and validation of an m6A RNA methylation regulator prognostic model for early‑stage clear cell renal cell carcinoma
TL;DR: In this article , a prognostic model consisting of m6A RNA methylation regulators in early stage clear cell renal cell carcinoma (ccRCC) was constructed and the reliability of the signature was assessed by proteomics and immunohistochemistry.
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