CircHIPK3通过调控p53-Akt-Mdm2通路影响食管鳞癌的恶性表型

目的 研究食管鳞癌组织中CircHIPK3的表达差异，以寻找食管鳞癌诊断和靶向治疗的新思路。方法 qRT-PCR、CCK-8法、Transwell法和流式细胞术检测CircHIPK3在食管鳞癌和癌旁组织中的表达差异以及其对细胞增殖、侵袭、迁移和凋亡的影响；生物信息数据分析确定CircHIPK3的可能作用通路，Western blot对其通路相关功能蛋白加以验证。结果 11例患者的癌组织和对应的7例癌旁组织中CircHIPK3表达异常（P=0.027）；CircHIPK3高表达的细胞增殖（P<0.001）、迁移（P<0.001）、侵袭（P<0.001）能力增强；CircHIPK3过表达的EC9706细胞凋亡受到抑制，抑癌基因p53被明显抑制，而Akt-Mdm2信号通路处于激活状态，p53-Akt-Mdm2通路蛋白的表达量随之增加，最终导致癌细胞增殖、迁移、侵袭以及相关癌症蛋白的表达增加。结论 CircHIPK3可能通过调节p53-Akt-Mdm2信号通路促进人食管鳞癌细胞的增殖、迁移和侵袭，并抑制细胞凋亡，其可能是食管鳞癌诊断和治疗的潜在靶点。

CircHIPK3 Affects Malignant Phenotypes in Esophageal Squamous Cell Carcinoma byRegulating p53-Akt-Mdm2 Signaling Pathways

Objective To investigate CircHIPK3 expression in esophageal squamous cell carcinoma (ESCC) tissues, so as to find a new way of diagnosis and targeted therapy. Methods qRT-PCR, CCK-8, Transwell and flow cytometry were performed to detect the difference of CircHIPK3 expression in tumor tissues and adjacent normal tissues, and its effect on cell proliferation, invasion, migration and apoptosis, respectively. Bioinformatics analysis was used to determine the possible pathway of CircHIPK3, and Western blot was used to verify its pathway-related functional proteins. Results qRT-PCR results showed the abnormal expression of CircHIPK3 in 11 cases of cancer tissues and 7 cases of paracancerous tissues (P=0.027). The high expression of CircHIPK3 increased cell proliferation (P<0.001), migration (P<0.001) and invasion (P<0.001) abilities. CircHIPK3 overexpression inhibited the apoptosis of EC9706 cells and tumor suppressor gene p53, activated intracellular Akt-Mdm2 signaling pathway, and increased the expression of p53-Akt-Mdm2 pathway protein accordingly. Ultimately, cancer cell proliferation, migration, invasion and cancer protein expression were enhanced. Conclusion CircHIPK3 promotes the proliferation, migration and invasion of human esophageal cancer cells, and inhibits the apoptosis by regulating the p53-Akt-Mdm2 signaling pathway. CircHIPK3 may be a potential target for the diagnosis and treatment of esophageal cancer.