The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer
Abstract Transcription factors (TFs) and long noncoding RNAs (lncRNAs) contribute to gastric cancer (GC). However, the roles of TFs and lncRNAs in the invasion and metastasis of GC remain largely unknown. Here, we observed that the transcription factor VAX2 is significantly upregulated in GC cells a...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01688-4 |
| _version_ | 1797578074620952576 |
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| author | Linjie Hong Ping Yang Luyu Zhang Xuehua Liu Xiangyang Wei Wushuang Xiao Zhen Yu Jieming Zhang Ying Peng Xiaosheng Wu Weimei Tang Fachao Zhi Guoxin Li Aimin Li Jianjiao Lin Side Liu Hui Zhang Li Xiang Jide Wang |
| author_facet | Linjie Hong Ping Yang Luyu Zhang Xuehua Liu Xiangyang Wei Wushuang Xiao Zhen Yu Jieming Zhang Ying Peng Xiaosheng Wu Weimei Tang Fachao Zhi Guoxin Li Aimin Li Jianjiao Lin Side Liu Hui Zhang Li Xiang Jide Wang |
| author_sort | Linjie Hong |
| collection | DOAJ |
| description | Abstract Transcription factors (TFs) and long noncoding RNAs (lncRNAs) contribute to gastric cancer (GC). However, the roles of TFs and lncRNAs in the invasion and metastasis of GC remain largely unknown. Here, we observed that the transcription factor VAX2 is significantly upregulated in GC cells and tissues and acts as an oncogene. Moreover, high VAX2 expression is associated with the advancement of tumors in GC. In terms of functionality, the enforced expression of VAX2 promotes the proliferation and metastasis of GC cells. Mechanistically, VAX2 specifically interacts with the LINC01189 promoter and represses LINC01189 transcription. Furthermore, LINC01189 exhibits significant downregulation in GC and functions as a suppressor gene. Functionally, it inhibits migratory and invasive abilities in GC cells. In the context of GC metastasis, VAX2 plays a role in modulating it by trans-repressing the expression of LINC01189. Additionally, LINC01189 binds to hnRNPF to enhance hnRNPF degradation through ubiquitination. The cooperation between LINC01189 and hnRNPF regulates GC cell invasion and migration. In addition, both VAX2 and hnRNPF are highly expressed, while LINC01189 is expressed in at low levels in GC tissues compared to normal gastric tissues. Our study suggests that VAX2 expression facilitates, while LINC01189 expression suppresses, metastasis and that the VAX2-LINC01189-hnRNPF axis plays a contributory role in GC development. |
| first_indexed | 2024-03-10T22:18:06Z |
| format | Article |
| id | doaj.art-1b0eb5f2f3454458af56395ed1fd22fd |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-10T22:18:06Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-1b0eb5f2f3454458af56395ed1fd22fd2023-11-19T12:22:18ZengNature Publishing GroupCell Death Discovery2058-77162023-10-019111310.1038/s41420-023-01688-4The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancerLinjie Hong0Ping Yang1Luyu Zhang2Xuehua Liu3Xiangyang Wei4Wushuang Xiao5Zhen Yu6Jieming Zhang7Ying Peng8Xiaosheng Wu9Weimei Tang10Fachao Zhi11Guoxin Li12Aimin Li13Jianjiao Lin14Side Liu15Hui Zhang16Li Xiang17Jide Wang18Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityDepartment of Gastroenterology, The Affiliated Hexian Memorial Hospital of Southern Medical UniversityDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityAbstract Transcription factors (TFs) and long noncoding RNAs (lncRNAs) contribute to gastric cancer (GC). However, the roles of TFs and lncRNAs in the invasion and metastasis of GC remain largely unknown. Here, we observed that the transcription factor VAX2 is significantly upregulated in GC cells and tissues and acts as an oncogene. Moreover, high VAX2 expression is associated with the advancement of tumors in GC. In terms of functionality, the enforced expression of VAX2 promotes the proliferation and metastasis of GC cells. Mechanistically, VAX2 specifically interacts with the LINC01189 promoter and represses LINC01189 transcription. Furthermore, LINC01189 exhibits significant downregulation in GC and functions as a suppressor gene. Functionally, it inhibits migratory and invasive abilities in GC cells. In the context of GC metastasis, VAX2 plays a role in modulating it by trans-repressing the expression of LINC01189. Additionally, LINC01189 binds to hnRNPF to enhance hnRNPF degradation through ubiquitination. The cooperation between LINC01189 and hnRNPF regulates GC cell invasion and migration. In addition, both VAX2 and hnRNPF are highly expressed, while LINC01189 is expressed in at low levels in GC tissues compared to normal gastric tissues. Our study suggests that VAX2 expression facilitates, while LINC01189 expression suppresses, metastasis and that the VAX2-LINC01189-hnRNPF axis plays a contributory role in GC development.https://doi.org/10.1038/s41420-023-01688-4 |
| spellingShingle | Linjie Hong Ping Yang Luyu Zhang Xuehua Liu Xiangyang Wei Wushuang Xiao Zhen Yu Jieming Zhang Ying Peng Xiaosheng Wu Weimei Tang Fachao Zhi Guoxin Li Aimin Li Jianjiao Lin Side Liu Hui Zhang Li Xiang Jide Wang The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer Cell Death Discovery |
| title | The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer |
| title_full | The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer |
| title_fullStr | The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer |
| title_full_unstemmed | The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer |
| title_short | The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer |
| title_sort | vax2 linc01189 hnrnpf signaling axis regulates cell invasion and migration in gastric cancer |
| url | https://doi.org/10.1038/s41420-023-01688-4 |
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