Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases
N6-methyladenosine (m6A) is a post-transcriptional RNA modification and one of the most abundant types of RNA chemical modifications. m6A functions as a molecular switch and is involved in a range of biomedical aspects, including cardiovascular diseases, the central nervous system, and cancers. Conc...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5815 |
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| author | Yazhen You Yundong Fu Mingjie Huang Dandan Shen Bing Zhao Hongmin Liu Yichao Zheng Lihua Huang |
| author_facet | Yazhen You Yundong Fu Mingjie Huang Dandan Shen Bing Zhao Hongmin Liu Yichao Zheng Lihua Huang |
| author_sort | Yazhen You |
| collection | DOAJ |
| description | N6-methyladenosine (m6A) is a post-transcriptional RNA modification and one of the most abundant types of RNA chemical modifications. m6A functions as a molecular switch and is involved in a range of biomedical aspects, including cardiovascular diseases, the central nervous system, and cancers. Conceptually, m6A methylation can be dynamically and reversibly modulated by RNA methylation regulatory proteins, resulting in diverse fates of mRNAs. This review focuses on m6A demethylases fat-mass- and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), which especially erase m6A modification from target mRNAs. Recent advances have highlighted that FTO and ALKBH5 play an oncogenic role in various cancers, such as acute myeloid leukemias (AML), glioblastoma, and breast cancer. Moreover, studies in vitro and in <i>mouse</i> models confirmed that FTO-specific inhibitors exhibited anti-tumor effects in several cancers. Accumulating evidence has suggested the possibility of FTO and ALKBH5 as therapeutic targets for specific diseases. In this review, we aim to illustrate the structural properties of these two m6A demethylases and the development of their specific inhibitors. Additionally, this review will summarize the biological functions of these two m6A demethylases in various types of cancers and other human diseases. |
| first_indexed | 2024-03-10T03:42:39Z |
| format | Article |
| id | doaj.art-8ee68289653348cbbc0ee7a3b4c0ee1f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:42:39Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ee68289653348cbbc0ee7a3b4c0ee1f2023-11-23T11:28:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310581510.3390/ijms23105815Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human DiseasesYazhen You0Yundong Fu1Mingjie Huang2Dandan Shen3Bing Zhao4Hongmin Liu5Yichao Zheng6Lihua Huang7Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, ChinaGreen Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, ChinaGreen Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaGreen Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, ChinaN6-methyladenosine (m6A) is a post-transcriptional RNA modification and one of the most abundant types of RNA chemical modifications. m6A functions as a molecular switch and is involved in a range of biomedical aspects, including cardiovascular diseases, the central nervous system, and cancers. Conceptually, m6A methylation can be dynamically and reversibly modulated by RNA methylation regulatory proteins, resulting in diverse fates of mRNAs. This review focuses on m6A demethylases fat-mass- and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), which especially erase m6A modification from target mRNAs. Recent advances have highlighted that FTO and ALKBH5 play an oncogenic role in various cancers, such as acute myeloid leukemias (AML), glioblastoma, and breast cancer. Moreover, studies in vitro and in <i>mouse</i> models confirmed that FTO-specific inhibitors exhibited anti-tumor effects in several cancers. Accumulating evidence has suggested the possibility of FTO and ALKBH5 as therapeutic targets for specific diseases. In this review, we aim to illustrate the structural properties of these two m6A demethylases and the development of their specific inhibitors. Additionally, this review will summarize the biological functions of these two m6A demethylases in various types of cancers and other human diseases.https://www.mdpi.com/1422-0067/23/10/5815m6A demethylasesFTOAKBH5human diseasesinhibitors |
| spellingShingle | Yazhen You Yundong Fu Mingjie Huang Dandan Shen Bing Zhao Hongmin Liu Yichao Zheng Lihua Huang Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases International Journal of Molecular Sciences m6A demethylases FTO AKBH5 human diseases inhibitors |
| title | Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases |
| title_full | Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases |
| title_fullStr | Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases |
| title_full_unstemmed | Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases |
| title_short | Recent Advances of m6A Demethylases Inhibitors and Their Biological Functions in Human Diseases |
| title_sort | recent advances of m6a demethylases inhibitors and their biological functions in human diseases |
| topic | m6A demethylases FTO AKBH5 human diseases inhibitors |
| url | https://www.mdpi.com/1422-0067/23/10/5815 |
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