PLOD2通过PI3K/AKT通路促进宫颈癌细胞增殖、侵袭和迁移

PLOD2 promotes the proliferation,invasion,and migration of cervical cancer cells through the PI3K/AKT pathway

目的:探讨赖氨酸羟化酶2(PLOD2)在宫颈鳞癌中的表达情况及其对宫颈鳞癌细胞增殖、侵袭和迁移能力的影响及机制。方法:通过生物信息学方法分析PLOD2在宫颈鳞癌组织中的表达及其与宫颈鳞癌临床病理特点的相关性。通过免疫组化和Western Blot方法检测PLOD2蛋白在宫颈鳞癌组织中的表达情况,并分析其与宫颈鳞癌临床病理特点的相关性。在宫颈SiHa、HeLa和H8细胞中,利用pLKO.1-shRNA质粒稳定干扰PLOD2基因表达情况,采用CCK8、平板克隆、划痕、Transwell侵袭实验检测PLOD2基因对宫颈鳞癌细胞增殖、迁移、侵袭能力的影响。通过Western Blot实验检测PLOD2对PI3K/AKT通路的影响,并在过表达PLOD2的情况下加入PI3K抑制剂进一步比较其增殖、迁移和侵袭能力及PI3K/AKT通路表达情况。结果:PLOD2蛋白在宫颈鳞癌组织及细胞中的蛋白表达量高于正常宫颈组织及细胞。结合生物信息学分析及临床标本免疫组化实验发现,宫颈鳞癌中PLOD2蛋白表达与患者组织分型、淋巴结转移、无病生存期有关(P<0.05)。PLOD2可以通过PI3K/AKT通路促进宫颈癌细胞增殖、侵袭和迁移。结论:PLOD2基因通过PI3K/AKT通路影响宫颈鳞癌的增殖、侵袭和迁移。

Objective:To analyze the expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2(PLOD2)in cervical cancer tissues and cells and to explore its carcinogenesis in cervical cancer.Methods:The PLOD2 expression of cervical cancer tissue were analyzed by bioinformatics methods.The relationship between PLOD2 expression and clinicopathologic characteristics of cervical squamous cell carcinoma was analyzed by Oncomine analysis.The PLOD2 expression was analyzed in HeLa cells,SiHa cells,and human cervical normal immortalized cells H8.After knocking down the expression of PLOD2 by using shRNA,we analyzed the ability of proliferation,migration,and invasion in cervical cancer cells by CCK8 assay,wound healing assay,and Transwell assay.The effect of PLOD2 on PI3K/AKT pathway was evaluated by Western Blot in vitro.In order to further illustrate the proliferation,migration,and invasion ability and the expression of PI3K-AKT pathway proteins,PI3K inhibitor was added to culture medium in the case of overexpression of PLOD2.Results:We observed that PLOD2 was highly expressed in cervical squamous cell carcinoma tissues and cells.The expression of PLOD2 had a strong correlation with histological subtype,nodal metastasis,and the prognosis of cervical squamous cell carcinoma.Patients with higher PLOD2 expression had shorter survival time than those with lower PLOD2 expression.Silencing the expression of PLOD2 sup pressed the proliferation,migration,and invasion of the cervical cancer cells.Moreover,experiments in vitro showed PLOD2 could promote the proliferation,invasion and migration of cervical cancer cells through PI3K/AKT pathway.Conclusion:The data obtained in this study showed that PLOD2 promoted the progress of cervical cancer via the PI3K/AKT pathway.