IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment
Summary: The acidic microenvironment is considered an important factor in colorectal cancer (CRC) that contributes to malignant transformation. However, the underlying mechanism remains unclear. In a previous study, we confirmed that IDH1 K224 deacetylation promotes enzymatic activity and the produc...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422301283X |
| _version_ | 1797774535458553856 |
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| author | Bo Wang Long Zhao Changjiang Yang Yilin Lin Shan Wang Yingjiang Ye Jianyuan Luo Zhanlong Shen |
| author_facet | Bo Wang Long Zhao Changjiang Yang Yilin Lin Shan Wang Yingjiang Ye Jianyuan Luo Zhanlong Shen |
| author_sort | Bo Wang |
| collection | DOAJ |
| description | Summary: The acidic microenvironment is considered an important factor in colorectal cancer (CRC) that contributes to malignant transformation. However, the underlying mechanism remains unclear. In a previous study, we confirmed that IDH1 K224 deacetylation promotes enzymatic activity and the production of α-KG. Here, we further investigate the effect of IDH1 hyperacetylation on the CRC acidic microenvironment. We demonstrate that increased α-KG affects hydroxylation of Ago2 and mediates miR-9-5p targeting NHE1 protein. Knockdown of NHE1 dramatically attenuates CRC cell proliferation and migration by restricting transport of intracellular H+ out of cells. Furthermore, we show that miR-9-5p is the microRNA with the most significant difference in the alteration of IDH1 K224 acetylation and can downregulate NHE1 mRNA. Our data also indicate that hydroxylation stabilizes Ago2, which in turn promotes miR-9-5p activity. Taken together, our results reveal a novel mechanism through which IDH1 deacetylation regulates the cellular acidic microenvironment and inhibits CRC metastasis. |
| first_indexed | 2024-03-12T22:21:31Z |
| format | Article |
| id | doaj.art-2c3439274a31401fab738650e68d7095 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:21:31Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-2c3439274a31401fab738650e68d70952023-07-23T04:55:56ZengElsevieriScience2589-00422023-07-01267107206IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironmentBo Wang0Long Zhao1Changjiang Yang2Yilin Lin3Shan Wang4Yingjiang Ye5Jianyuan Luo6Zhanlong Shen7Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. ChinaDepartment of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. ChinaDepartment of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. ChinaDepartment of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. ChinaDepartment of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. ChinaDepartment of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. ChinaDepartment of Medical Genetics, Peking University Health Science Center, Beijing 100191, P.R. ChinaDepartment of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People’s Hospital, No.11 Xizhimen South Street, Beijing 100044, P.R. China; Corresponding authorSummary: The acidic microenvironment is considered an important factor in colorectal cancer (CRC) that contributes to malignant transformation. However, the underlying mechanism remains unclear. In a previous study, we confirmed that IDH1 K224 deacetylation promotes enzymatic activity and the production of α-KG. Here, we further investigate the effect of IDH1 hyperacetylation on the CRC acidic microenvironment. We demonstrate that increased α-KG affects hydroxylation of Ago2 and mediates miR-9-5p targeting NHE1 protein. Knockdown of NHE1 dramatically attenuates CRC cell proliferation and migration by restricting transport of intracellular H+ out of cells. Furthermore, we show that miR-9-5p is the microRNA with the most significant difference in the alteration of IDH1 K224 acetylation and can downregulate NHE1 mRNA. Our data also indicate that hydroxylation stabilizes Ago2, which in turn promotes miR-9-5p activity. Taken together, our results reveal a novel mechanism through which IDH1 deacetylation regulates the cellular acidic microenvironment and inhibits CRC metastasis.http://www.sciencedirect.com/science/article/pii/S258900422301283XCell biologyCancer |
| spellingShingle | Bo Wang Long Zhao Changjiang Yang Yilin Lin Shan Wang Yingjiang Ye Jianyuan Luo Zhanlong Shen IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment iScience Cell biology Cancer |
| title | IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment |
| title_full | IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment |
| title_fullStr | IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment |
| title_full_unstemmed | IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment |
| title_short | IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment |
| title_sort | idh1 k224 acetylation promotes colorectal cancer via mir 9 5p nhe1 axis mediated regulation of acidic microenvironment |
| topic | Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S258900422301283X |
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