OpenLB Open Library of Bioscience

Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers.

Xiaonan Liu, Pei Wang, Xufei Teng, Zhang Zhang, Shuhui Song
Author Information
  1. Xiaonan Liu: National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China.
  2. Pei Wang: National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China.
  3. Xufei Teng: National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China.
  4. Zhang Zhang: National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China.
  5. Shuhui Song: National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China.

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 studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.
RESULTS: Here we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that , , and were down-regulated in most cancers, whereas and were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/ and hsa-miR-204-5p/) that could serve a critical role for potential clinical application in KIRC patients.
CONCLUSIONS: Our findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators' expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.

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RESULTS: characterized expression profiles RNA m6A regulators 13 cancer types Cancer Genome Atlas TCGA data showed down-regulated cancers whereas up-regulated 12 cancer types except thyroid carcinoma THCA Survival analysis revealed low expression several m6A regulators displayed longer overall survival times analyzed microRNA miRNA -regulated DNA methylation-regulated expression changes m6A regulators pan-cancer total identified 158 miRNAs 58 DNA methylation probes DMPs involved expression regulation RNA m6A regulators Furthermore assessed survival significance regulatory pairs Among 10 miRNAs 7 DMPs may promote cancer initiation progression conversely 3 miRNA/mRNA pairs kidney renal clear cell carcinoma KIRC may exert tumor-suppressor function findings indicative potential prognostic values Finally validated two miRNA/mRNA pairs hsa-miR-1307-3p/ hsa-miR-204-5p/ serve critical role potential clinical application KIRC patients.
CONCLUSIONS: findings highlighted importance upstream regulation miRNA DNA methylation governing m6A regulators' expression pan-cancer result identified several informative regulatory pairs prognostic stratification Thus study provides new insights molecular mechanisms m6A modification human cancers.
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