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N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification

N6-methyladenosine (m(6)A) serves as the most common and conserved internal transcriptional modification. However, the roles of m(6)A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely c...

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Autores principales: Wang, Qianqing, Guo, Xiangcui, Li, Li, Gao, Zhihui, Su, Xiaoke, Ji, Mei, Liu, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585578/
https://www.ncbi.nlm.nih.gov/pubmed/33099572
http://dx.doi.org/10.1038/s41419-020-03071-y
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author Wang, Qianqing
Guo, Xiangcui
Li, Li
Gao, Zhihui
Su, Xiaoke
Ji, Mei
Liu, Juan
author_facet Wang, Qianqing
Guo, Xiangcui
Li, Li
Gao, Zhihui
Su, Xiaoke
Ji, Mei
Liu, Juan
author_sort Wang, Qianqing
collection PubMed
description N6-methyladenosine (m(6)A) serves as the most common and conserved internal transcriptional modification. However, the roles of m(6)A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m(6)A profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3’-Untranslated Region (3’-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a m(6)A reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m(6)A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.
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spelling pubmed-75855782020-10-26 N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification Wang, Qianqing Guo, Xiangcui Li, Li Gao, Zhihui Su, Xiaoke Ji, Mei Liu, Juan Cell Death Dis Article N6-methyladenosine (m(6)A) serves as the most common and conserved internal transcriptional modification. However, the roles of m(6)A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m(6)A profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3’-Untranslated Region (3’-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a m(6)A reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m(6)A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment. Nature Publishing Group UK 2020-10-24 /pmc/articles/PMC7585578/ /pubmed/33099572 http://dx.doi.org/10.1038/s41419-020-03071-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Qianqing
Guo, Xiangcui
Li, Li
Gao, Zhihui
Su, Xiaoke
Ji, Mei
Liu, Juan
N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
title N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
title_full N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
title_fullStr N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
title_full_unstemmed N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
title_short N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification
title_sort n(6)-methyladenosine mettl3 promotes cervical cancer tumorigenesis and warburg effect through ythdf1/hk2 modification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585578/
https://www.ncbi.nlm.nih.gov/pubmed/33099572
http://dx.doi.org/10.1038/s41419-020-03071-y
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