目的：探讨肝细胞癌（HCC）患者血清及癌组织中miR-203a和其靶基因的表达及其与患者临床病理特征和预后的关系。方法：利用生物信息学方法从TargetScan、miRDB 和PicTar 网站预测HCC组织中miR-203a的靶基因，通过双荧光素酶报告基因实验进行验证。选取2018 年1月至2019 年6月在常州市金坛区第二人民医院手术切除的96例HCC患者的癌和癌旁组织标本、血清和临床资料，以及90 例健康体检者的血清作为对照。qPCR 法检测血清miR-203a 水平，以及HCC 组织和癌旁组织中miR-203a及其靶基因表达，比较分析不同临床病理特征HCC患者miR-203a及其靶基因表达。随访3年，采用Kaplan-Meier法进行生存（OS）分析。结果：从数据库筛选出HCC中miR-203a相关的靶基因共10个，包括APC、CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PAQR3、PRMT5 和SOSC3。HCC 组织中miR-203a 和APC、PAQR3 mRNA 表达水平均显著低于癌旁组织（均P<0.01），CDK6、 GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PRMT5 和 SOSC3 mRNA表达水平均显著高于癌旁组织（均P<0.01）；血清miR-203a、 HCC组织miR-203a及其靶基因表达均与患者肿瘤临床分期、分化程度、肝功能分级、OS率有关（均P<0.01）。结论：HCC组织中miR-203a呈低表达，miR-203a及靶基因表达均与患者肿瘤临床分期、分化程度、肝功能及远期OS率有关。

Objective: To investigate the expressions of miR-203a and its target genes in serum and tumor tissues of patients with hepatocellular carcinoma (HCC) and their relationships with clinicopathological characteristics and prognosis. Methods: The target genes of miR-203a were predicted from TargetScan, miRDB and PicTar websites using bioinformatics methods, which were verified by double luciferase gene report experiment. The samples of cancer tissues and para-cancerous tissues, serum and clinical data of 96 patients with HCC whose tumors were surgically removed at the Second People's Hospital of Jintan District, Changzhou City from January 2018 to June 2019 were collected. The serum of 90 healthy people was collected as controls. The serum miR-203a level and the expressions of miR-203a and its target genes in HCC and para-cancerous tissues were detected by qPCR. The expressions of miR-203a and its target genes in HCC patients with different clinicopathological characteristics were comparatively analyzed. The patients were followed-up for 3 years and overall survival (OS) analysis was performed by Kaplan-Meier method. Results: A total of 10 miR-203a-related target genes were screened from databases, including adenomatous polyposis coli (APC), cyclin dependent kinase 6 (CDK6), transcription factor GATA binding protein 6 (GATA6), homeobox D3 (HOXD3), insulin-like growth factor class 1 receptor (IGF1R), insulin-like growth factor binding protein-5 (IGFBP5), potassium intermediate small conductance calcium activated channel subfamily N, member2 (KCNE2), progestin and adipoQ receptor 3 (PAQR3), Protein arginine methyltransferase 5 (PRMT5) and suppressor of cytokine signaling 3 (SOSC3). The expressions of miR-203a, APC and PAQR3 mRNA in the HCC tissues were significantly lower than those in the para-cancerous tissues (all P<0.01), and the expressions of CDK6, GATA6, HOXD3, IGF1R, IGFBP5, KCNE2、PRMT5 and SOSC3 mRNA were significantly higher than those in the para-cancerous tissues (all P<0.01). The expressions of serum miR-203a and miR-203a and its target genes in HCC tissues were related to the clinical stage, differentiation degree, liver function grade and OS rate of the patients (all P<0.01). Conclusion: miR-203a in HCC tissues is in low expression, and the expressions of miR-203a and target genes are related to clinical stage, differentiation, liver function and long-term OS rate.

国家重点研发计划“国家质量基础的共性技术研究与应用”重点专项（No. 2019YFF0216502）