Abstract：
Cervical cancer (CC) is the primary cancer-related cause of morbidity and mortality in women. Previous studies have shown that placenta-specific 8 (PLAC8) has different functions in multiple malignancies. This study aimed to explore the function and regulatory mechanism of PLAC8 in CC. Bioinformatics and immunohistochemical analyses demonstrated that PLAC8 was significantly upregulated in CC tissues compared with normal tissues. Gain/loss-of-function experiments showed that siRNA-mediated knockdown of PLAC8 suppressed cell migration and invasion, while PLAC8 overexpression promoted cell motility. Moreover, PLAC8 was revealed to affect the epithelial-mesenchymal transition (EMT) process by upregulating epithelial (E)-cadherin and decreasing the expression of mesenchymal markers of EMT, including vimentin, zinc finger E-box binding homeobox 1 (ZEB1), neural (N)-cadherin, matrix metalloproteinase-9 (MMP-9), and MMP-2 in PLAC8-silenced cells. PLAC8 activated the AKT pathway, as proven by the downregulation of p-AKTSer473 and p-AKTThr308 expression after PLAC8 knockdown. Furthermore, PLAC8 overexpression upregulated the expression of sex-determining region Y-related high-mobility group box transcription factor 4 (SOX4), which is reported to mediate the activation of the AKT pathway, and SOX4 deficiency reversed the cellular functions caused by PLAC8 overexpression. Overall, the present study indicates that PLAC8 may facilitate CC development by activating the SOX4-mediated AKT pathway, suggesting that PLAC8 may serve as a potential biomarker for CC treatment.
摘要：
宫颈癌（CC）是女性发病和死亡的主要癌症相关原因。先前的研究表明，胎盘特异性8（PLAC8）在多种恶性肿瘤中具有不同的功能。本研究旨在探讨PLAC8在CC中的功能及调控机制。生物信息学和免疫组织化学分析表明，与正常组织相比，PLAC8在CC组织中明显上调。功能增益/丧失实验表明，siRNA介导的PLAC8敲低抑制细胞迁移和侵袭，而PLAC8过表达促进细胞运动。此外，PLAC8被揭示通过上调上皮（E）-钙黏着蛋白和降低EMT的间充质标志物的表达来影响上皮-间质转化（EMT）过程，包括波形蛋白,锌指E盒绑定homeobox1(ZEB1),神经（N）-钙黏着蛋白，基质金属蛋白酶-9(MMP-9),PLAC8沉默细胞中的MMP-2。PLAC8激活了AKT通路，正如PLAC8敲低后p-AKTSer473和p-AKTThr308表达下调所证明的那样。此外，PLAC8过表达上调性别决定区Y相关高迁移率族盒转录因子4(SOX4)的表达,据报道，它介导AKT途径的激活，和SOX4缺乏逆转了PLAC8过表达引起的细胞功能。总的来说,本研究表明，PLAC8可能通过激活SOX4介导的AKT通路促进CC的发展，提示PLAC8可能作为CC治疗的潜在生物标志物。
