METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression
Abstract Background Splicing factor B subunit 4 (SF3B4) has been confirmed to participate in the progression of many cancers and is considered to be a potential target for non‐small cell lung cancer (NSCLC). Thus, the role and molecular mechanism of SF3B4 in NSCLC progression deserves further study....
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.15275 |
| _version_ | 1797208959323471872 |
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| author | Guangsi He Kangsheng Gu Jie Wei Jian Zhang |
| author_facet | Guangsi He Kangsheng Gu Jie Wei Jian Zhang |
| author_sort | Guangsi He |
| collection | DOAJ |
| description | Abstract Background Splicing factor B subunit 4 (SF3B4) has been confirmed to participate in the progression of many cancers and is considered to be a potential target for non‐small cell lung cancer (NSCLC). Thus, the role and molecular mechanism of SF3B4 in NSCLC progression deserves further study. Methods Quantitative real‐time PCR and western blot were employed to detect the mRNA and protein levels of SF3B4, Sm‐like protein 4 (LSM4) and methyltransferase‐like 3 (METTL3). Cell proliferation, apoptosis, invasion, migration and stemness were tested by cell counting kit‐8, colony formation, flow cytometry, transwell, wound healing, and sphere formation assays. The interaction between SF3B4 and METTL3 or LSM4 was confirmed by MeRIP, RIP and Co‐IP assays. Mice xenograft models were constructed to assess the effects of METTL3 and SF3B4 on NSCLC tumorigenesis. Results SF3B4 had high expression in NSCLC tissues and was associated with the shorter overall survival of NSCLC patients. Knockdown of SF3B4 suppressed NSCLC cell proliferation, invasion, migration and stemness, while inducing apoptosis. METTL3 promoted SF3B4 mRNA stability by m6A modification, and its knockdown inhibited NSCLC cell growth, metastasis and stemness by downregulating SF3B4. SF3B4 could interact with LSM4, and sh‐SF3B4‐mediated the inhibition on NSCLC cell functions could be reversed by LSM4 overexpression. In addition, reduced METTL3 expression restrained NSCLC tumor growth, and this effect was reversed by SF3B4 overexpression. Conclusion METTL3‐stablized SF3B4 promoted NSCLC cell growth, metastasis and stemness via positively regulating LSM4. |
| first_indexed | 2024-04-24T09:47:05Z |
| format | Article |
| id | doaj.art-ddad363dfe3240c6a25b5a77cc930017 |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-04-24T09:47:05Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-ddad363dfe3240c6a25b5a77cc9300172024-04-15T01:29:47ZengWileyThoracic Cancer1759-77061759-77142024-04-01151191992810.1111/1759-7714.15275METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expressionGuangsi He0Kangsheng Gu1Jie Wei2Jian Zhang3Department of Oncology the First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Oncology the First Affiliated Hospital of Anhui Medical University Hefei ChinaFirst Department of Oncology First People's Hospital of Chuzhou Chuzhou ChinaSecond Department of Oncology First People's Hospital of Chuzhou Chuzhou ChinaAbstract Background Splicing factor B subunit 4 (SF3B4) has been confirmed to participate in the progression of many cancers and is considered to be a potential target for non‐small cell lung cancer (NSCLC). Thus, the role and molecular mechanism of SF3B4 in NSCLC progression deserves further study. Methods Quantitative real‐time PCR and western blot were employed to detect the mRNA and protein levels of SF3B4, Sm‐like protein 4 (LSM4) and methyltransferase‐like 3 (METTL3). Cell proliferation, apoptosis, invasion, migration and stemness were tested by cell counting kit‐8, colony formation, flow cytometry, transwell, wound healing, and sphere formation assays. The interaction between SF3B4 and METTL3 or LSM4 was confirmed by MeRIP, RIP and Co‐IP assays. Mice xenograft models were constructed to assess the effects of METTL3 and SF3B4 on NSCLC tumorigenesis. Results SF3B4 had high expression in NSCLC tissues and was associated with the shorter overall survival of NSCLC patients. Knockdown of SF3B4 suppressed NSCLC cell proliferation, invasion, migration and stemness, while inducing apoptosis. METTL3 promoted SF3B4 mRNA stability by m6A modification, and its knockdown inhibited NSCLC cell growth, metastasis and stemness by downregulating SF3B4. SF3B4 could interact with LSM4, and sh‐SF3B4‐mediated the inhibition on NSCLC cell functions could be reversed by LSM4 overexpression. In addition, reduced METTL3 expression restrained NSCLC tumor growth, and this effect was reversed by SF3B4 overexpression. Conclusion METTL3‐stablized SF3B4 promoted NSCLC cell growth, metastasis and stemness via positively regulating LSM4.https://doi.org/10.1111/1759-7714.15275LSM4METTL3non‐small cell lung cancerSF3B4 |
| spellingShingle | Guangsi He Kangsheng Gu Jie Wei Jian Zhang METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression Thoracic Cancer LSM4 METTL3 non‐small cell lung cancer SF3B4 |
| title | METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression |
| title_full | METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression |
| title_fullStr | METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression |
| title_full_unstemmed | METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression |
| title_short | METTL3‐mediated the m6A modification of SF3B4 facilitates the development of non‐small cell lung cancer by enhancing LSM4 expression |
| title_sort | mettl3 mediated the m6a modification of sf3b4 facilitates the development of non small cell lung cancer by enhancing lsm4 expression |
| topic | LSM4 METTL3 non‐small cell lung cancer SF3B4 |
| url | https://doi.org/10.1111/1759-7714.15275 |
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