SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52 |
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| Authors: | Yuchao Diao Yingwei Li Zixiang Wang Shourong Wang Peng Li Beihua Kong |
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| Affiliation: | 1.Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012 China ;2.Department of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, 266000 Shangdong China ;3.School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012 China |
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| Abstract: | Many studies have proven that splicing factors are crucial for human malignant tumor development. However, as a classical splicing factor, the expression of SF3B4 is not clear, and its biological function needs to be further clarified in ovarian cancer (OC). We determined that SF3B4 was obviously upregulated and its high expression was associated with poor prognosis in OC patients. In vitro and in vivo assays suggested that SF3B4 overexpression promoted OC cell proliferation and mobility, and downregulation of SF3B4 had the opposite effect. Further studies found that miR-509–3p decreased SF3B4 mRNA expression by binding to the 3’ -UTR of SF3B4 directly. Importantly, we revealed that RAD52 was a potential target of SF3B4 through alternative splicing events analysis. Loss of SF3B4 led to decreased expression of RAD52, owing to intron 8 retention and generation of premature termination codons. Moreover, decreased expression of RAD52 partially counteracted the tumor-promoting effect of SF3B4 overexpression. In conclusion, our results suggested that SF3B4, negatively regulated by miR-509–3p, promoted OC progression through effective splicing of RAD52. Therefore, SF3B4 may be a promising biomarker and effective therapeutic target for OC.Subject terms: Ovarian cancer, Prognostic markers |
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