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METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.
METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 Dec 20; Vol. 146, pp. 113780. Date of Electronic Publication: 2024 Dec 20. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Esophageal cancer is a major malignancy with a high incidence and poor prognosis. To elucidate the mechanisms underlying its progression, particularly with respect to cell division and spindle orientation, we investigated the role of m6A modifications and the centrosomal protein CEP170. Using m6A-seq and RNA-seq of esophageal cancer tissues and adjacent normal tissues, we identified significant alterations in m6A modifications and gene expression, highlighting the upregulation and m6A enrichment of CEP170 in tumor tissues. Functional assays, including cell cycle synchronization, qPCR, immunoblotting, immunofluorescence, coimmunoprecipitation, methylated RNA immunoprecipitation, and cell proliferation assays, demonstrated that CEP170 plays a critical role in mitotic progression and spindle orientation. m6A-seq and RNA-seq revealed significant alterations in m6A modifications and gene expression in esophageal cancer. CEP170 was upregulated and highly enriched in m6A modifications in tumor tissues. Functional assays revealed that CEP170 plays a critical role in proper mitotic progression and spindle orientation. Knockdown of CEP170 led to spindle misorientation and impaired the stability of astral microtubules. Additionally, CEP170 affected the localization of the dynein/dynactin motor complex in the cell cortex. METTL3 was upregulated in tumor tissues and regulated CEP170 expression. RNA-seq upon CEP170 depletion revealed that ASPM was significantly downregulated, indicating its involvement as a downstream target of CEP170 in regulating cell proliferation and mitosis. Our findings provide novel insights into the molecular mechanisms by which CEP170 and m6A modifications regulate esophageal cancer progression, revealing that CEP170 is a potential therapeutic target.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024. Published by Elsevier B.V.)
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 146
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39708485
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.113780