Yang Huichun, Ma Xuejuan, Song Baoping, Wang Dan, Chai Zeying
Department of Obstetrics and Gynecology, Taizhou Hospital, Wenzhou Medical University, Linhai City Taizhou, China.
Department of Obstetrics and Gynecology, Taizhou Hospital, Wenzhou Medical University, Linhai City Taizhou, China
Ann Clin Lab Sci. 2023 Sep;53(5):738-748.
Cervical cancer (CC) is one of the fatal malignancies affecting the life expectancy of women worldwide. Golgi Phosphoprotein 3 (GOLPH3) has been shown to play a key role in the development of various tumors. However, the role of GOLPH3 in the development of CC is unclear.
GOLPH3 levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Xenograft tumor models were used to explore the effects of GOLPH3 on tumor growth of mice, and immunohistochemistry assay was performed to determine the expression of GOLPH3 and Ki-67. Transwell assay was performed to evaluate cell migration and invasion. Western blot assay was used to analyze the signaling molecules-related proteins regulated by GOLPH3.
GOLPH3 was upregulated in human CC tissues from the GEO database (GSE39001 and GSE63514), and further demonstrated that GOLPH3 level was elevated in human CC cells. GOLPH3 enhanced CC cell proliferation, and knockdown of GOLPH3 suppressed tumor growth and decreased Ki-67 level in xenograft mice. In addition, GOLPH3 aggravated the migration and invasion of CC cells. The data indicated that Wnt/β-catenin signaling might be one of the key targets of GOLPH3. Blockage of the Wnt/β-catenin pathway by XAV-939 significantly affected the effects of GOLPH3 on cell proliferation and epithelial-mesenchymal transition (EMT) related molecules, whereas LiCl (a Wnt/β-catenin signal activator) reversed these above effects.
GOLPH3 promotes cell proliferation, migration and invasion in CC, possibly by regulating the Wnt/β-catenin signaling pathway, which may provide a new idea for the development of CC therapeutic targets.
宫颈癌（CC）是影响全球女性预期寿命的致命恶性肿瘤之一。高尔基体磷蛋白3（GOLPH3）已被证明在多种肿瘤的发生发展中起关键作用。然而，GOLPH3在CC发生发展中的作用尚不清楚。
采用定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测GOLPH3水平。使用细胞计数试剂盒-8（CCK-8）和集落形成试验检测细胞增殖。采用异种移植肿瘤模型探讨GOLPH3对小鼠肿瘤生长的影响，并进行免疫组织化学检测以确定GOLPH3和Ki-67的表达。采用Transwell试验评估细胞迁移和侵袭能力。用蛋白质免疫印迹法分析受GOLPH3调控的信号分子相关蛋白。
从基因表达综合数据库（GEO数据库，GSE39001和GSE63514）中发现，GOLPH3在人CC组织中上调，进一步证实GOLPH3在人CC细胞中水平升高。GOLPH3促进CC细胞增殖，敲低GOLPH3可抑制异种移植小鼠的肿瘤生长并降低Ki-67水平。此外，GOLPH3加剧了CC细胞的迁移和侵袭。数据表明，Wnt/β-连环蛋白信号通路可能是GOLPH3的关键靶点之一。XAV-939阻断Wnt/β-连环蛋白通路显著影响GOLPH3对细胞增殖和上皮-间质转化（EMT）相关分子的作用，而氯化锂（一种Wnt/β-连环蛋白信号激活剂）可逆转上述作用。
GOLPH3可能通过调节Wnt/β-连环蛋白信号通路促进CC细胞增殖、迁移和侵袭，这可能为CC治疗靶点的开发提供新思路。
