邹艳丽.微小RNA-125a-5p对胰腺癌细胞吉西他滨耐药的影响[J].内科急危重症杂志,2025,31(4):370-373
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DOI:10.11768/nkjwzzzz20250417 |
中文关键词: 胰腺癌 微小RNA-125a-5p 吉西他滨 耐药 |
英文关键词: |
基金项目:武汉市卫健委科研项目(WX20Q17);武汉市卫健委科研项目(WX23Z20) |
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中文摘要: |
摘要 目的:检测胰腺癌(PC)组织及PC细胞系中微小RNA(miRNA,miR)-125a-5p的表达及其对PC细胞吉西他滨(Gem)耐药性的影响。方法:收集13对PC及对应癌旁组织标本;构建PC Gem耐药细胞系;实时荧光定量聚合酶链反应(qRT-PCR)验证所有样本miR-125a-5p的表达;通过癌症基因组图谱(TCGA)数据库对PC患者的生存预后进行差异分析;转染miR-125a-5p模拟物(mimic)及抑制剂,细胞计数试剂盒-8(CCK-8)检测PC细胞Gem的半数抑制浓度(IC50),探讨miR-125a-5p对细胞耐药的影响。数据库预测miR-125a-5p的靶基因,蛋白印迹法检测miR-125a-5p对信号转导和转录激活因子3(STAT3)蛋白表达的影响。结果:PC组织miR-125a-5p的表达显著低于癌旁组织,PC细胞系miR-125a-5p的表达较正常胰腺细胞明显降低。miR-125a-5p与PC患者的生存预后密切相关。miR-125a-5p在Gem处理的PC细胞表达下调。与非耐药细胞比较,耐药细胞miR-125a-5p的表达明显减低。CCK-8结果显示转染miR-125a-5p 模拟物后细胞的IC50值显著降低,转染miR-125a-5p抑制剂后细胞的IC50值显著升高。过表达miR-125a-5p抑制STAT3蛋白的表达。结论:miR-125a-5p在PC中表达降低,并与PC患者生存预后相关,miR-125a-5p可能通过抑制STAT3介导PC Gem耐药。 |
英文摘要: |
Abstract Objective: To detect the expression of microRNA (miRNA, miR)-125a-5p in pancreatic cancer (PC) tissues and cell lines and its effect on gemcitabine (Gem) resistance of PC cells. Methods: A total of 13 pairs of PC and adjacent non-cancer tissue samples were collected. Gem resistant PC cell lines were constructed. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression level of miR-125a-5p in all samples. The Cancer Genome Atlas (TCGA) database was used to analyze the differential prognosis of PC patients. Cell counting kit-8 (CCK-8) was used to detect the half inhibitory concentration (IC50) of Gem in PC cells after transfection with miR-125a-5p mimic or inhibitor, to investigate the effect of miR-125a-5p on drug resistance of cells. The database was used to predict the target genes of miR-125a-5p, and Western blotting was employed to examine the effect of miR-125a-5p on the expression of signal transducer and activator of transcription 3 (STAT3) protein. Results: The expression of miR-125a-5p in the PC tissue was significantly lower than that in the adjacent cancerous tissue. The expression of miR-125a-5p in PC cell lines was significantly lower than that in the normal control cells. Expression of miR-125a-5p was closely related to the prognosis of PC patients. Expression of miR-125a-5p was down-regulated in PC cells treated with Gem. Compared with non-drug resistant cells, the expression of miR-125a-5p was significantly reduced in drug resistant cells. CCK-8 data showed that the IC50 value of cells was significantly decreased after transfection with miR-125a-5p mimic, while the IC50 value was significantly increased after transfection with miR-125a-5p inhibitor. Overexpression of miR-125a-5p inhibited the expression of STAT3 protein. Conclusions: The miR-125a-5p is low expression in PC cells and correlated with the survival prognosis of PC patients. The miR-125a-5p may mediate the Gem resistance of PC cells by inhibiting STAT3. |
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