Xiaonan Liu1,2, Pei Wang1,3, Xufei Teng1,3, Zhang Zhang1,2,3,4, Shuhui Song1,3,4. 1. National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China. 2. School of Future Technology, University of Chinese Academy of Sciences, Beijing, China. 3. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China. 4. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, 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 METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 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/METTL14 and hsa-miR-204-5p/IGF2BP3) 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.
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 METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 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/METTL14 and hsa-miR-204-5p/IGF2BP3) 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.
Authors: Ann M Bailey; Le Zhan; Dipen Maru; Imad Shureiqi; Curtis R Pickering; Galina Kiriakova; Julie Izzo; Nan He; Caimiao Wei; Veerabhadran Baladandayuthapani; Han Liang; Scott Kopetz; Garth Powis; Grace L Guo Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-10-31 Impact factor: 4.052
Authors: Philip Knuckles; Tina Lence; Irmgard U Haussmann; Dominik Jacob; Nastasja Kreim; Sarah H Carl; Irene Masiello; Tina Hares; Rodrigo Villaseñor; Daniel Hess; Miguel A Andrade-Navarro; Marco Biggiogera; Mark Helm; Matthias Soller; Marc Bühler; Jean-Yves Roignant Journal: Genes Dev Date: 2018-03-13 Impact factor: 11.361