Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma
Abstract Background Epigenetic alterations have been shown to contribute immensely to human carcinogenesis. Dynamic and reversible N6‐methyladenosine (m6A) RNA modification regulates gene expression and cell fate. However, the reasons for activation of KIAA1429 (also known as VIRMA, an RNA methyltra...
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Cancer Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cac2.12325 |
| _version_ | 1818118108438593536 |
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| author | Chang Zhang Qi Sun Xu Zhang Na Qin Zhening Pu Yayun Gu Caiwang Yan Meng Zhu Juncheng Dai Cheng Wang Ni Li Guangfu Jin Hongxia Ma Zhibin Hu Erbao Zhang Fengwei Tan Hongbing Shen |
| author_facet | Chang Zhang Qi Sun Xu Zhang Na Qin Zhening Pu Yayun Gu Caiwang Yan Meng Zhu Juncheng Dai Cheng Wang Ni Li Guangfu Jin Hongxia Ma Zhibin Hu Erbao Zhang Fengwei Tan Hongbing Shen |
| author_sort | Chang Zhang |
| collection | DOAJ |
| description | Abstract Background Epigenetic alterations have been shown to contribute immensely to human carcinogenesis. Dynamic and reversible N6‐methyladenosine (m6A) RNA modification regulates gene expression and cell fate. However, the reasons for activation of KIAA1429 (also known as VIRMA, an RNA methyltransferase) and its underlying mechanism in lung adenocarcinoma (LUAD) remain largely unexplored. In this study, we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD. Methods Whole‐genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase. The in vitro and in vivo functions of KIAA1429 were investigated. Transcriptome sequencing, methylated RNA immunoprecipitation sequencing (MeRIP‐seq), m6A dot blot assays and RNA immunoprecipitation (RIP) were performed to confirm the modified gene mediated by KIAA1429. RNA stability assays were used to detect the half‐life of the target gene. Results Copy number amplification drove higher expression of KIAA1429 in LUAD, which was correlated with poor overall survival. Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD. Mechanistically, the target genes of KIAA1429‐mediated m6A modification were confirmed by transcriptome sequencing and MeRIP‐seq assays. We also revealed that KIAA1429 could regulate BTG2 expression in an m6A‐dependent manner. Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA, leading to enhanced YTH m6A RNA binding protein 2 (YTHDF2, the m6A “reader”)‐dependent BTG2 mRNA stability and promoted the expression of BTG2; thus, participating in the tumorigenesis of LUAD. Conclusions Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis, which may provide a novel view on the targeted molecular therapy of LUAD. |
| first_indexed | 2024-12-11T04:49:04Z |
| format | Article |
| id | doaj.art-7f270e629ebf42e6a90092fac46b9748 |
| institution | Directory Open Access Journal |
| issn | 2523-3548 |
| language | English |
| last_indexed | 2024-12-11T04:49:04Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Communications |
| spelling | doaj.art-7f270e629ebf42e6a90092fac46b97482022-12-22T01:20:27ZengWileyCancer Communications2523-35482022-07-0142760962610.1002/cac2.12325Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinomaChang Zhang0Qi Sun1Xu Zhang2Na Qin3Zhening Pu4Yayun Gu5Caiwang Yan6Meng Zhu7Juncheng Dai8Cheng Wang9Ni Li10Guangfu Jin11Hongxia Ma12Zhibin Hu13Erbao Zhang14Fengwei Tan15Hongbing Shen16Department of Epidemiology School of Public Health Southeast University Nanjing Jiangsu 210009 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaCenter of Clinical Research Wuxi People's Hospital of Nanjing Medical University Wuxi Jiangsu 214023 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Epidemiology Center for Global Health School of Public Health Nanjing Medical University Nanjing Jiangsu 211166 P. R. ChinaDepartment of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 P. R. ChinaDepartment of Epidemiology School of Public Health Southeast University Nanjing Jiangsu 210009 P. R. ChinaAbstract Background Epigenetic alterations have been shown to contribute immensely to human carcinogenesis. Dynamic and reversible N6‐methyladenosine (m6A) RNA modification regulates gene expression and cell fate. However, the reasons for activation of KIAA1429 (also known as VIRMA, an RNA methyltransferase) and its underlying mechanism in lung adenocarcinoma (LUAD) remain largely unexplored. In this study, we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD. Methods Whole‐genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase. The in vitro and in vivo functions of KIAA1429 were investigated. Transcriptome sequencing, methylated RNA immunoprecipitation sequencing (MeRIP‐seq), m6A dot blot assays and RNA immunoprecipitation (RIP) were performed to confirm the modified gene mediated by KIAA1429. RNA stability assays were used to detect the half‐life of the target gene. Results Copy number amplification drove higher expression of KIAA1429 in LUAD, which was correlated with poor overall survival. Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD. Mechanistically, the target genes of KIAA1429‐mediated m6A modification were confirmed by transcriptome sequencing and MeRIP‐seq assays. We also revealed that KIAA1429 could regulate BTG2 expression in an m6A‐dependent manner. Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA, leading to enhanced YTH m6A RNA binding protein 2 (YTHDF2, the m6A “reader”)‐dependent BTG2 mRNA stability and promoted the expression of BTG2; thus, participating in the tumorigenesis of LUAD. Conclusions Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis, which may provide a novel view on the targeted molecular therapy of LUAD.https://doi.org/10.1002/cac2.12325BTG2gene amplificationKIAA1429LUADmRNA stabilityN6‐methyladenosine |
| spellingShingle | Chang Zhang Qi Sun Xu Zhang Na Qin Zhening Pu Yayun Gu Caiwang Yan Meng Zhu Juncheng Dai Cheng Wang Ni Li Guangfu Jin Hongxia Ma Zhibin Hu Erbao Zhang Fengwei Tan Hongbing Shen Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma Cancer Communications BTG2 gene amplification KIAA1429 LUAD mRNA stability N6‐methyladenosine |
| title | Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma |
| title_full | Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma |
| title_fullStr | Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma |
| title_full_unstemmed | Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma |
| title_short | Gene amplification‐driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A‐YTHDF2‐dependent in lung adenocarcinoma |
| title_sort | gene amplification driven rna methyltransferase kiaa1429 promotes tumorigenesis by regulating btg2 via m6a ythdf2 dependent in lung adenocarcinoma |
| topic | BTG2 gene amplification KIAA1429 LUAD mRNA stability N6‐methyladenosine |
| url | https://doi.org/10.1002/cac2.12325 |
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