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HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner
N6-methyladenosine (m6A) RNA methylation has been determined to execute crucial functions in tumorigenesis and cancer development. WT1-associated protein (WTAP) has an important “writer” role in m6A modification, and it is also a nuclear protein that colocalizes with splicing factors and plays a cri...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207020/ https://www.ncbi.nlm.nih.gov/pubmed/35733918 http://dx.doi.org/10.1155/2022/6130806 |
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author | Lyu, Yuanyuan Zhang, Yilin Wang, Yuhan Luo, Yonghong Ding, Huafeng Li, Peiling Ni, Guantai |
author_facet | Lyu, Yuanyuan Zhang, Yilin Wang, Yuhan Luo, Yonghong Ding, Huafeng Li, Peiling Ni, Guantai |
author_sort | Lyu, Yuanyuan |
collection | PubMed |
description | N6-methyladenosine (m6A) RNA methylation has been determined to execute crucial functions in tumorigenesis and cancer development. WT1-associated protein (WTAP) has an important “writer” role in m6A modification, and it is also a nuclear protein that colocalizes with splicing factors and plays a critical role in cell function and cancer progression. However, little is known about the role of WTAP in ovarian cancer (OC) and its mechanisms. In this study, we found for the first time that hypoxia-inducible factor (HIF)-1α could positively regulate increased expression of WTAP under hypoxia. And further results revealed that WTAP expression was closely associated with the clinicopathological features of OC, and high expression of WTAP predicted low survival rate in patients with OC. In addition, cell proliferation and invasive capacity were significantly reduced after knockdown of WTAP expression in OC cells. However, cell proliferation and invasive ability were significantly enhanced after overexpression of WTAP. Additionally, we find that WTAP interacts with DGCR8 (a crucial chip protein) to regulate the expression of microRNA-200 (miR-200) in an m6A-dependent way. Further experiments showed that the key glycolysis enzyme HK2 could be positively regulated by miR-200, which significantly affected the intracellular Warburg effect. In conclusion, this is considered uncovered that upregulation of WTAP expression by HIF-1α intercedes with miRNA processing, accelerates the Warburg impact, and advances the event and advancement of tumor, thus giving a novel viewpoint on m6A adjustment in OC movement. |
format | Online Article Text |
id | pubmed-9207020 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-92070202022-06-21 HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner Lyu, Yuanyuan Zhang, Yilin Wang, Yuhan Luo, Yonghong Ding, Huafeng Li, Peiling Ni, Guantai J Immunol Res Research Article N6-methyladenosine (m6A) RNA methylation has been determined to execute crucial functions in tumorigenesis and cancer development. WT1-associated protein (WTAP) has an important “writer” role in m6A modification, and it is also a nuclear protein that colocalizes with splicing factors and plays a critical role in cell function and cancer progression. However, little is known about the role of WTAP in ovarian cancer (OC) and its mechanisms. In this study, we found for the first time that hypoxia-inducible factor (HIF)-1α could positively regulate increased expression of WTAP under hypoxia. And further results revealed that WTAP expression was closely associated with the clinicopathological features of OC, and high expression of WTAP predicted low survival rate in patients with OC. In addition, cell proliferation and invasive capacity were significantly reduced after knockdown of WTAP expression in OC cells. However, cell proliferation and invasive ability were significantly enhanced after overexpression of WTAP. Additionally, we find that WTAP interacts with DGCR8 (a crucial chip protein) to regulate the expression of microRNA-200 (miR-200) in an m6A-dependent way. Further experiments showed that the key glycolysis enzyme HK2 could be positively regulated by miR-200, which significantly affected the intracellular Warburg effect. In conclusion, this is considered uncovered that upregulation of WTAP expression by HIF-1α intercedes with miRNA processing, accelerates the Warburg impact, and advances the event and advancement of tumor, thus giving a novel viewpoint on m6A adjustment in OC movement. Hindawi 2022-06-12 /pmc/articles/PMC9207020/ /pubmed/35733918 http://dx.doi.org/10.1155/2022/6130806 Text en Copyright © 2022 Yuanyuan Lyu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Lyu, Yuanyuan Zhang, Yilin Wang, Yuhan Luo, Yonghong Ding, Huafeng Li, Peiling Ni, Guantai HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner |
title | HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner |
title_full | HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner |
title_fullStr | HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner |
title_full_unstemmed | HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner |
title_short | HIF-1α Regulated WTAP Overexpression Promoting the Warburg Effect of Ovarian Cancer by m6A-Dependent Manner |
title_sort | hif-1α regulated wtap overexpression promoting the warburg effect of ovarian cancer by m6a-dependent manner |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207020/ https://www.ncbi.nlm.nih.gov/pubmed/35733918 http://dx.doi.org/10.1155/2022/6130806 |
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