ALKBH5 activates CEP55 transcription through m6A demethylation in FOXP2 mRNA and expedites cell cycle entry and EMT in ovarian cancer.

Autor: Yu J; Department of Obstetrics and Gynecology, Taizhou Hospital Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang Province, 317000, China., Chen X; Department of Obstetrics and Gynecology, Taizhou Hospital Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang Province, 317000, China., Ding X; Department of Hematologic Oncology, Taizhou Central Hospital, (Taizhou University Hospital), Taizhou, Zhejiang Province, 318000, China., Lin K; Department of Obstetrics and Gynecology, Taizhou Hospital Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang Province, 317000, China., Zhang T; Department of Obstetrics and Gynecology, Taizhou Hospital Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang Province, 317000, China., Wang K; Department of Obstetrics and Gynecology, Taizhou Hospital Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang Province, 317000, China. wangk7683@enzemed.com.
Jazyk: angličtina
Zdroj: Biology direct [Biol Direct] 2024 Nov 07; Vol. 19 (1), pp. 105. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1186/s13062-024-00551-5
Abstrakt: Background: Centrosomal protein of 55 kDa (CEP55) overexpression has been linked to tumor stage, aggressiveness of the tumor, poor prognosis, and metastasis. This study aims to elucidate the action of CEP55 in ovarian cancer (OC) and the regulation by the alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5)/Forkhead box protein P2 (FOXP2) axis.
Methods: Differentially expressed genes in OC were identified using in silico identification, followed by prognostic value assessment. Lentiviral vectors were constructed to downregulate CEP55 in OC cells, and colony formation, EdU, TUNEL, flow cytometry, Transwell assays, and Phalloidin staining were conducted. Transcription factors regulating CEP55 were predicted and verified, and rescue experiments were performed. The effect of ALKBH5-mediated demethylation on FOXP2 mRNA stability and OC cell cycle and EMT were analyzed.
Results: High expression of CEP55 in OC was linked to unsatisfactory prognosis of patients. Knockdown of CEP55 repressed proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) while inducing apoptosis and cell cycle arrest in OC cells. FOXP2 bound to the promoter of CEP55 to repress CEP55 transcription. FOXP2 regulated transcriptional repression of CEP55 to impede the malignant progression of OC and inhibit tumor metastasis. ALKBH5-mediated demethylation modification induced mRNA degradation of FOXP2. Knockdown of ALKBH5 induced cell cycle arrest and inhibited EMT in OC cells.
Conclusions: ALKBH5 hinders FOXP2-mediated transcriptional repression of CEP55 to promote the malignant progression of OC via cell cycle and EMT.
(© 2024. The Author(s).)
Databáze: MEDLINE
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