目的:卵巢癌(OC)是妇科恶性肿瘤死亡的主要原因,其病因和发病机制目前尚不清楚。最近的研究发现PUF60在各种癌症中过度表达。然而,PUF60在全局RNA加工中的确切功能及其在OC中的作用尚不清楚。
方法:采用多数据库分析和免疫组化方法分析PUF60的表达及其与临床特征的关系。通过体外细胞增殖试验检测PUF60对卵巢癌细胞增殖和转移的表型效应,迁移测定,体内异种移植模型和肺转移模型。RNA免疫沉淀,海马分析,RNA稳定性分析用于研究PUF60对OC中氧化磷酸化(OXPHOS)相关基因稳定性的影响。
结果:我们报告PUF60在OC中高表达,频繁扩增高达33.9%,其上调预测预后不良。PUF60在体外和体内均促进OC细胞的增殖和迁移。机械上,我们证明了PUF60的沉默增强了参与OXPHOS的mRNA转录本的稳定性,并减少了加工体(P体)的形成,最终提高OXPHOS水平。
结论:我们的研究揭示了PUF60在OC能量代谢中的新功能。因此,PUF60可作为治疗OC患者的新靶点。
OBJECTIVE: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that
PUF60 overexpressed in various cancers. However, the exact function of
PUF60 in global RNA processing and its role in OC has been unclear.
METHODS: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC.
RESULTS: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis.
PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level.
CONCLUSIONS: Our study unveils a novel function of
PUF60 in OC energy metabolism. Thus,
PUF60 may serve as a novel target for the treatment of patients with OC.