THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification
Abstract The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carci...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06008-3 |
| _version_ | 1797769330779226112 |
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| author | Tao Yu Qi Zhang Shao-Kun Yu Feng-Qi Nie Mei-Ling Zhang Qian Wang Kai-Hua Lu |
| author_facet | Tao Yu Qi Zhang Shao-Kun Yu Feng-Qi Nie Mei-Ling Zhang Qian Wang Kai-Hua Lu |
| author_sort | Tao Yu |
| collection | DOAJ |
| description | Abstract The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3′UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC. |
| first_indexed | 2024-03-12T21:07:26Z |
| format | Article |
| id | doaj.art-cd6bb7052d894a17b89f14e85905b0f6 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-12T21:07:26Z |
| publishDate | 2023-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-cd6bb7052d894a17b89f14e85905b0f62023-07-30T11:25:49ZengNature Publishing GroupCell Death and Disease2041-48892023-07-0114711310.1038/s41419-023-06008-3THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modificationTao Yu0Qi Zhang1Shao-Kun Yu2Feng-Qi Nie3Mei-Ling Zhang4Qian Wang5Kai-Hua Lu6Department of Oncology, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, the Second Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, the First Affiliated Hospital of Nanjing Medical UniversityAbstract The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3′UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC.https://doi.org/10.1038/s41419-023-06008-3 |
| spellingShingle | Tao Yu Qi Zhang Shao-Kun Yu Feng-Qi Nie Mei-Ling Zhang Qian Wang Kai-Hua Lu THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification Cell Death and Disease |
| title | THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification |
| title_full | THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification |
| title_fullStr | THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification |
| title_full_unstemmed | THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification |
| title_short | THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification |
| title_sort | thoc3 interacts with ybx1 to promote lung squamous cell carcinoma progression through pfkfb4 mrna modification |
| url | https://doi.org/10.1038/s41419-023-06008-3 |
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