目的：探讨miR-203a-3p对胰腺癌BxPC-3细胞增殖、迁移和侵袭能力的影响。方法：运用癌症基因组图谱（TCGA） 数据库筛选胰腺癌组织和癌旁组织中差异表达的miRNA，分析miRNA高表达与低表达时胰腺癌患者的生存率和临床分期；利用 TarBase数据库分析miRNA与癌症相关的GO功能与KEGG通路，利用DIANA Tools、miRDB和TargetScan网站预测miR-203a-3p 的靶基因。将miR-203a-3p mimic及NC mimic、miR-203a-3p inhibitor及NC inhibitor转染至BxPC-3细胞，用qPCR法检测胰腺癌 细胞和胰腺正常上皮细胞HPNE中miR-203a-3p、miR-192-5p和miR-451a表达水平，以CCK-8法、Transwell小室法和克隆形成实 验分别检测BxPC-3细胞的增殖、迁移、侵袭和集落形成能力。结果：通过TCGA数据库筛选出18个胰腺癌组织中差异表达的 miRNA，其中miR-203a-3p、miR-192-5p、miR-451a具有物种保守性 ，且其与胰腺癌临床癌症分期、细胞周期和患者生存率相 关（均P<0.05）；生物信息学网站预测显示miR-203a-3p的候选靶基因是PPM1A，PPM1A与多基因存在相互作用。miR-203a-3p、 miR-192-5p和miR-451a在BxPC-3和Aspc-1细胞中均高表达（均P<0.01）。miR-203a-3p mimic组BxPC-3细胞中miR-203a-3p表 达水平以及细胞增殖、迁移和侵袭能力均显著提高（均P<0.01）：miR-203a-3p inhibitor组细胞中miR-203a-3p表达水平以及细胞 增殖、迁移和侵袭能力均显著降低（均P<0.01）。结论：miR-203a-3p在胰腺癌组织及细胞中均高表达，其表达与患者生存和临床 分期相关，可调控BxPC-3细胞的增殖、迁移和侵袭能力。
Objective: To investigate the effects of miR-203a-3p on the proliferation, migration and invasion ability of pancreatic cancer BxPC-3 cells. Methods: The Cancer Genome Atlas (TCGA) database was used to screen the differentially expressed miRNAs between pancreatic cancer tissues and paracancerous tissues, and to analyze the survival rate and clinical stage of pancreatic cancer patients with high or low miRNA expression; TarBase was used for the cancer related GO function and KEGG pathway analysis of the miRNAs, DIANATools, miRDB and TargetScan websites were used to predict the target genes of miR-203a-3p. miR-203a-3p mimic and NC mimic, miR-203a-3p inhibitor and NC inhibitor were transfected into BxPC-3 cells. The expression levels of miR-203a-3p, miR-192-5p and miR-451a in normal pancreatic epithelial HPNE cells and pancreatic cancer cells were detected by qPCR. The proliferation, migration, invasion and colony formation abilities of BxPC-3 cells were detected by CCK-8, Transwell chamber assay and Colony formation assay, respectively. Results: A total of 18 differentially expressed miRNAs in pancreatic cancer tissues were screened out by TCGA database, among which miR-203a3p, miR-192-5p and miR-451a were species-conservative and significantly correlated with clinical cancer stage, cell cycle and survival rate of pancreatic cancer patients (all P<0.05); Bioinformatics tool predicted that PPM1A might be the candidate target gene of miR 203a-3p and could interact with multiple genes. miR-203a-3p, miR-192-5p and miR-451a were highly expressed in BxPC-3 and Aspc cells (all P<0.001). In miR-203a-3p mimic group, the expression level of miR-203a-3p and the proliferation, migration and invasion ability of BxPC-3 cells were significantly increased (all P<0.01); however, in miR-203a-3p inhibitor group, the expression level of miR-203a-3p and the ability of cell proliferation, migration and invasion were significantly decreased (all P<0.01). Conclusion: miR-203a-3p is highly expressed in pancreatic cancer tissues and cells, and its expression is related to the survival and clinical stage of patients. miR-203a-3p may regulate the proliferation, migration and invasion of BxPC-3 cells.
国家自然科学青年基金资助项目（No.81201281）；2020年政府资助临床医学优秀人才培养项目（No.冀财预复397号）；河北省 唐山市科学技术研究与发展计划（No.19130204C）；河北省省属高等学校基本科研业务费研究项目（No. JQN2020005）；河北省重点研发计划项目 （No.213777115D）；华北理工大学大学生创新创业训练计划（No.X2020083）