He YingYing, He Zhicheng, Zhang Xiaoyu, Liu Shubai
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, #132 Lanhei Road, Panlong District, Kunming, 650201, Yunnan, People's Republic of China.
School of Chemical Science & Technology, Yunnan University, Kunming, 650091, Yunnan, China.
Cancer Cell Int. 2021 Dec 20;21(1):697. doi: 10.1186/s12935-021-02406-9.
Ovarian cancer is the leading cause of death from gynaecologic illnessed worldwide. Platelet-activating factor acetyl hydrolase IB2 (PAF-AH IB2) is an intracellular serine esterase that hydrolyzes platelet-activating factor, a G-protein-like trimer with two catalytic subunits and one regulatory subunit. The regulatory role of PAF-AH IB2 in the oncogenesis of ovarian cancer is not well understood.
In this study, the TCGA dataset and clinical cancer tissue microarray were utilized to investigate abnormal overexpression of PAF-AH IB2 in ovarian cancer. To investigate the impact on the cell proliferation, migration, and tumorigenicity in vitro, PAF-AH IB2 stable knocking down (KD) ovarian cancer cells were established by ShRNA. The whole transcription profiling, tyrosine kinase profiling and standard cell functional assays were integrated to explore the biological importance and mechanism of PAF-AH IB2 modulated in ovarian cancer.
PAF-AH IB2 was identified significantly overexpression in four subtypes of ovarian cancer. In vitro, PAF-AH IB2 KD significantly inhibited cancer cell proliferation, migration, and tumorigenicity, activated caspases and caused cell cycle arrest, and made the cells more sensitive to PAF. PAF-AH 1B2 KD cells down-regulated several key regulators of the multiple tyrosine kinases-mediated signaling pathway, suggesting a novel interaction network between the growth factor receptors pathway and PAF-AH 1B2 mediated PAF signalling.
These findings revealed a previously undiscovered role for PAF-AH IB2 as a potenial therapy target and essential signaling mediators in ovarian cancer pathogenesis, as well as new possible preventive and therapeutic strategies to inhibit this enzyme in clinical treatment for ovarian cancer.
卵巢癌是全球妇科疾病致死的主要原因。血小板活化因子乙酰水解酶IB2（PAF-AH IB2）是一种细胞内丝氨酸酯酶，可水解血小板活化因子，血小板活化因子是一种具有两个催化亚基和一个调节亚基的G蛋白样三聚体。PAF-AH IB2在卵巢癌发生过程中的调节作用尚不清楚。
在本研究中，利用TCGA数据集和临床癌症组织芯片来研究PAF-AH IB2在卵巢癌中的异常过表达。为了研究其对体外细胞增殖、迁移和致瘤性的影响，通过短发夹RNA（ShRNA）建立了PAF-AH IB2稳定敲低（KD）的卵巢癌细胞系。整合全转录谱分析、酪氨酸激酶谱分析和标准细胞功能分析，以探讨PAF-AH IB2在卵巢癌中调控的生物学重要性及机制。
在卵巢癌的四种亚型中均发现PAF-AH IB2显著过表达。在体外，PAF-AH IB2敲低显著抑制癌细胞增殖、迁移和致瘤性，激活半胱天冬酶并导致细胞周期停滞，使细胞对PAF更敏感。PAF-AH 1B2敲低的细胞下调了多个酪氨酸激酶介导的信号通路的几个关键调节因子，提示生长因子受体通路与PAF-AH 1B2介导的PAF信号之间存在新的相互作用网络。
这些发现揭示了PAF-AH IB2在卵巢癌发病机制中作为潜在治疗靶点和重要信号介质的先前未被发现的作用，以及在卵巢癌临床治疗中抑制该酶的新的可能的预防和治疗策略。
