MicroRNA-92a 在胰腺癌中的表达及对肿瘤生长的影响

目的??探讨人胰腺导管腺癌（PDAC）中 microRNA-92a（miR-92a）的表达及对肿瘤细胞生长的影响。方法??实时荧光定量聚合酶链反应（qRT-PCR）检测 PDAC 组织中 miR-92a 的表达水平 ； 慢病毒转染 PANC-1 细胞构建 miR-92a 稳定敲除模型，克隆形成与流式细胞仪检测细胞增殖凋亡 ； 通过裸鼠皮下种植瘤模型检测下调 miR-92a 表达对肿瘤体内生长的影响 ； PCR 及 Western?blotting 检测 miR-92a 下游靶点DOC-2/DAB2 结合蛋白（DAB2IP）在体外培养细胞中的表达水平 ； 免疫组织化学检测 DAB2IP 在移植瘤组织中的表达水平。结果??miR-92a 在 PDAC 组织中表达水平高于癌旁组织（ P ?<0.05） ； miR-92a 高表达的胰PDAC 者肿瘤体积较 miR-92a 低表达者更大（ P ?<0.05） ； 下调 miR-92a 的表达能够抑制胰腺癌 PANC-1 细胞体外增殖能力，促进细胞凋亡，并抑制 PANC-1 细胞裸鼠皮下种植瘤的生长 ； 下调 miR-92a 表达提高了PANC-1 细胞内 DAB2IP 的表达水平及移植瘤组织内 DAB2IP 的表达水平（ P ?<0.05） 。结论??miR-92a 在胰腺癌中表达升高， 下调 miR-92a 的表达能使 DAB2IP 的表达下调而发挥抗肿瘤生长作用。

Effect of microRNA-92a on pancreatic ductal adenocarcinoma

Objective To investigate the expression and effect of MicroRNA-92a on pancreatic ductaladenocarcinoma (PDAC). Methods The expression of MicroRNA-92a in PDAC was detected by qRT-PCR.MicroRNA-92a inhibitory lentivirus was utilized for establishment of MicroRNA-92a knockdown model inPANC-1 cells. Clone formation assay and flow cytometry were performed for cell proliferation and apoptosis. Asubcutaneous xenotransplanted tumor model was conducted to investigate the effect of MicroRNA-92a on tumorgrowth in vivo. Expression of DAB2IP and MicroRNA-92a in mice tumor tissues were identified by Western blots orimmunohistochemical (IHC). Results MicroRNA-92a was up-regulated in PDAC tissues (P < 0.05). Knockdownof MicroRNA-92a suppressed cellular proliferation (P < 0.05) while enhanced apoptosis rate (t =5.840, P = 0.029)in PANC-1 cells. Down-regulation of MicroRNA-92a inhibited in vivo tumor growth (P < 0.05). Moreover, deletionof MicroRNA-92a induced increased expression of DAB2IP in vitro (P < 0.05) and in vivo (P < 0.05). Conclusions MicroRNA-92a facilitates PDAC tumor growth probably through activating DAB2IP.