摘要
目的 检测环状RNA hsa_circ_0128298在肝细胞肝癌(hepatocellular carcinama,HCC)中的表达,评价其参与HCC生长过程中的功能。方法 qPCR法检测50例HCC癌组织与相应的癌旁组织以及HCC细胞中hsa_circ_0128298的表达水平;采用CCK-8试验、流式细胞术、western blot等方法分析hsa_circ_0128298对HCC细胞增殖的影响;ROC曲线及生存曲线分析其在HCC诊断及预后中的价值。结果 与癌旁组织比较,hsa_circ_0128298在HCC癌组织中的表达显著升高( U =846.0, P = 0.005 );hsa_circ_0128298筛查HCC的ROC曲线下面积(AUC ROC )为0.661,95%置信区间( CI )为0.560~0.753,敏感性为 80.0%,特异性为50.0%。hsa_circ_0128298高表达的HCC患者总生存时间明显低于hsa_circ_0128298低表达者(χ 2=6.294, P = 0.012)。RNA干扰hsa_circ_0128298(si-hsa_circ_0128298)可显著抑制HCC细胞增殖,诱导细胞周期G 0/G 1期阻滞,同时可诱导细胞周期蛋白 p21 mRNA及蛋白质表达上调;而si-p21可逆转si-hsa_circ_0128298引起的HCC细胞增殖抑制及细胞周期阻滞,恢复其生长增殖潜能。结论 hsa_circ_0128298在HCC中高表达,可通过调节p21的表达促进HCC的生长,有望成为HCC诊断与治疗的新靶点。
Objective To investigate the expression of circular RNA hsa_circ_0128298 in hepatocellular harcinoma (HCC) and evaluate its function in the growth process of HCC. Methods qPCR was used to detect the expressions of hsa_circ_0128298 in 50 HCC tissues, corresponding paracancerous tissues and HCC cells. The effects of hsa_circ_0128298 on HCC growth was analyzed by CCK-8 kit, flow cytometry and western blot assays. The values of hsa_circ_0128298 for the diagnosis and prognosis of HCC were assessed by ROC curve and survival curve analyses. Results Compared with the paracancerous tissues, the expression of hsa_circ_0128298 was significantly increased in HCC tissues ( U =846.0, P =0.005). The area under ROC curve (AUC ROC ) was 0.661, 95% confidence interval ( CI ) was 0.560 to 0.753, sensitivity was 80.0% and specificity was 50.0%. HCC patients with high expression of hsa_circ_0128298 displayed less overall survival time than those with low expression of hsa_circ_0128298 (χ 2=6.294, P =0.012). RNA interference of hsa_circ_0128298 (si-hsa_circ_0128298) significantly inhibited HCC cell proliferation and induced cell cycle arrest at G 0/G 1, and also induced mRNA upregulation and protein expression of cyclin p21. Meanwhile,si-p21 partially reversed the proliferation inhibition and cell cycle arrest of HCC cells induced by si-hsa_circ_0128298, and restore its growth and proliferation potential. Conclusion The highly expressed hsa_circ_0128298 in HCC could promote the growth of HCC by regulating the expression of p21 and promise to be a new target for diagnosis and treatment of HCC.
作者
李祎
孔明珠
朱百惠
陈琳
蔡卫华
鞠少卿
王峰
LI Yi;KONG Mingzhu;ZHU Baihui;CHEN Lin;CAI Weihua;JU Shaoqing;WANG Feng(Department of Laboratory Medicine,Affiliated Hospital of Nantong University,Nantong 226001,Jiangsu;Department of Laboratory Medicine,School of Public Health,Nantong University,Nantong 226019,Jiangsu;Department of Laboratory Medicine,Nantong Third Hospital Affiliated to Nantong University,Nantong 226006,Jiangsu,China)
出处
《临床检验杂志》
CAS
2019年第8期568-573,共6页
Chinese Journal of Clinical Laboratory Science
基金
国家自然科学基金(81873978)
中国博士后基金项目(2018M642298)
江苏省社会发展项目(BE2019691)
江苏省大学生创新计划项目(201910304034Z)
南通市科技局项目(MS22018010)