CRKL在肝内胆管癌中的表达及对癌细胞增殖和侵袭的影响

Expression of CRKL in intrahepatic cholangiocarcinoma and its effect on the proliferation and invasion of cholangiocarci⁃noma cells

目的:研究激酶样基因CT10调节因子(CRKL)在肝内胆管癌(ICC)中的表达,及其对胆管癌细胞增殖与侵袭的影响。方法:采用qRT-PCR技术检测ICC组织和癌旁组织中CRKL的转录水平;利用免疫组织化学技术检测ICC组织和癌旁组织中CRKL的表达,分析其与临床病理特征的关系;通过siRNA技术抑制QBC939细胞中CRKL的表达,采用Western blot检测CRKL沉默对AKT及ERK信号通路的影响;MTT实验、细胞克隆形成实验及Transwell实验用于分析CRKL对ICC细胞的增殖和侵袭能力的影响。结果:ICC组织内CRKL表达上调,不同肿瘤大小、淋巴结转移及TNM分期等临床病理特征的ICC,其CRKL表达差异有统计学意义(P<0.05)。细胞实验显示,抑制CRKL后,AKT和ERK的磷酸化水平显著下降,ICC细胞的增殖和侵袭能力明显减弱(P<0.05)。结论:CRKL通过AKT和ERK信号途径促进肿瘤细胞的生长与侵袭,这可能为ICC的靶向治疗提供新的分子靶标和方向。

Objective:To investigate the expression of kinase-like gene CT10 regulatory factor(CRKL)in intrahepatic cholangiocarcinoma(ICC)and its effect on the proliferation and invasion of intrahepatic cholangiocarcinoma cells.Methods:qRT-PCR detected CRKL transcription in ICC patient tissues and adjacent tissues.Immunohistochemistry assessed CRKL expression in ICC tissues and adjacent tissues,and analyzed its relationship with clinicopathological features.For the inhibition of CRKL expression in QBC939 cells by siRNA technology,the effect of CRKL silencing on AKT and ERK signaling pathway was measured by Western blot.CRKL's influence on QBC939 cell prolifera-tion and invasion was analyzed by MTT,clonogenesis,and Transwell assays.Results:The expres-sion of CRKL in ICC tissues was up-regulated,and there were statistically significant differences in CRKL expression in ICC with different clinicopathological features such as tumor size,lymph node metastasis and TNM stage.Cellular experiments showed a significant decrease in the phosphoryla-tion of AKT and ERK upon inhibition of CRKL,and the proliferation and invasion ability of ICC cells was significantly diminished(P<0.05).Conclusion:CRKL promotes ICC cell proliferation and invasion through AKT and ERK pathways,offering new molecular targets and directions for targeted therapy.