N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression
Abstract Primary cilia are microtubule‐based organelles that function as cellular antennae to address multiple metabolic and extracellular cues. The past decade has seen significant advances in understanding the pro‐tumorigenic role of N6‐methyladenosine (m6A) modification in tumorigenesis. Neverthe...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408488 |
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| author | Yalan Rui Haisheng Zhang Kangning Yu Shiyao Qiao Chenglin Gao Xiansong Wang Weifeng Yang Gholamreza Asadikaram Zigang Li Kun Zhang Jianxin Peng Jiexin Li Junming He Hongsheng Wang |
| author_facet | Yalan Rui Haisheng Zhang Kangning Yu Shiyao Qiao Chenglin Gao Xiansong Wang Weifeng Yang Gholamreza Asadikaram Zigang Li Kun Zhang Jianxin Peng Jiexin Li Junming He Hongsheng Wang |
| author_sort | Yalan Rui |
| collection | DOAJ |
| description | Abstract Primary cilia are microtubule‐based organelles that function as cellular antennae to address multiple metabolic and extracellular cues. The past decade has seen significant advances in understanding the pro‐tumorigenic role of N6‐methyladenosine (m6A) modification in tumorigenesis. Nevertheless, whether m6A modification modulates the cilia dynamics during cancer progression remains unclear. Here, the results show that m6A methyltransferase METTL3 regulates cilia length in cancer cells via HDAC6‐dependent deacetylation of axonemal α‐tubulin, thereby controlling cancer development. Mechanically, METTL3 positively regulates the translation of HDAC6 in an m6A‐dependent manner, while m6A methylation of A3678 in the coding sequence (CDS) of HDAC6 ameliorates its translation efficiency via facilitating the binding with YTHDF3. The upregulation of HDAC6 induced by METTL3 over‐expression is capable of inhibiting cilia elongation and acetylation of α‐tubulin, thereby shortening cilia length and accelerating the progression of cervical cancer both in vitro and in vivo. Collectively, depletion of METTL3‐mediated m6A modification leads to abnormally elongated cilia via suppressing HDAC6‐dependent deacetylation of axonemal α‐tubulin, ultimately attenuating cell growth and cervical cancer development. |
| format | Article |
| id | doaj-art-8e049956b8a34461b344cfa64e5da80f |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8e049956b8a34461b344cfa64e5da80f2025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202408488N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 ExpressionYalan Rui0Haisheng Zhang1Kangning Yu2Shiyao Qiao3Chenglin Gao4Xiansong Wang5Weifeng Yang6Gholamreza Asadikaram7Zigang Li8Kun Zhang9Jianxin Peng10Jiexin Li11Junming He12Hongsheng Wang13Guangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaEndocrinology and Metabolism Research Center Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences Medical University Campus Kerman 7616913555 IranInstitute of Systems and Physical Biology Shenzhen Bay Laboratory Shenzhen 518067 ChinaThe Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 Hospital Chengdu Seventh People's Hospital Affiliated Cancer Hospital of Chengdu Medical College School of Biological Sciences and Technology Chengdu Medical College Chengdu 610500 ChinaDepartment of Hepatobiliary Surgery Guangdong Province Traditional Chinese Medical Hospital Guangzhou 510120 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaDepartment of Hepatobiliary Surgery Guangdong Province Traditional Chinese Medical Hospital Guangzhou 510120 ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 ChinaAbstract Primary cilia are microtubule‐based organelles that function as cellular antennae to address multiple metabolic and extracellular cues. The past decade has seen significant advances in understanding the pro‐tumorigenic role of N6‐methyladenosine (m6A) modification in tumorigenesis. Nevertheless, whether m6A modification modulates the cilia dynamics during cancer progression remains unclear. Here, the results show that m6A methyltransferase METTL3 regulates cilia length in cancer cells via HDAC6‐dependent deacetylation of axonemal α‐tubulin, thereby controlling cancer development. Mechanically, METTL3 positively regulates the translation of HDAC6 in an m6A‐dependent manner, while m6A methylation of A3678 in the coding sequence (CDS) of HDAC6 ameliorates its translation efficiency via facilitating the binding with YTHDF3. The upregulation of HDAC6 induced by METTL3 over‐expression is capable of inhibiting cilia elongation and acetylation of α‐tubulin, thereby shortening cilia length and accelerating the progression of cervical cancer both in vitro and in vivo. Collectively, depletion of METTL3‐mediated m6A modification leads to abnormally elongated cilia via suppressing HDAC6‐dependent deacetylation of axonemal α‐tubulin, ultimately attenuating cell growth and cervical cancer development.https://doi.org/10.1002/advs.202408488acetylated α‐tubulincilia lengthHDAC6m6Acervical cancer |
| spellingShingle | Yalan Rui Haisheng Zhang Kangning Yu Shiyao Qiao Chenglin Gao Xiansong Wang Weifeng Yang Gholamreza Asadikaram Zigang Li Kun Zhang Jianxin Peng Jiexin Li Junming He Hongsheng Wang N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression Advanced Science acetylated α‐tubulin cilia length HDAC6 m6A cervical cancer |
| title | N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression |
| title_full | N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression |
| title_fullStr | N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression |
| title_full_unstemmed | N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression |
| title_short | N6‐Methyladenosine Regulates Cilia Elongation in Cancer Cells by Modulating HDAC6 Expression |
| title_sort | n6 methyladenosine regulates cilia elongation in cancer cells by modulating hdac6 expression |
| topic | acetylated α‐tubulin cilia length HDAC6 m6A cervical cancer |
| url | https://doi.org/10.1002/advs.202408488 |
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