microRNA-140通过下调HDAC4抑制胃癌细胞迁移和侵袭能力  

MicroRNA-140 suppresses the migration and invasion potential of gastric cancer cell through downregulating HDAC4

作　　者：王显艳[1] 高峰[2] 赵春明[1] 孙玉荣[1] 温秋婷[1] 于秀文[1] 张晓杰[1] 

机构地区：[1]齐齐哈尔医学院病理学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院第三附属医院麻醉科,黑龙江齐齐哈尔1610060

出　　处：《癌症进展》2016年第3期223-227,共5页Oncology Progress

基　　金：黑龙江省教育厅科学技术研究面上项目(12531804)

摘　　要：目的探讨micro RNA-140(mi R-140)对胃癌细胞SGC-7901迁移及侵袭能力的影响及其调控机制。方法将mi R-140 mimics(mi R-140)、mi R-140特异性抑制剂(Anti-mi R-140)和针对HDAC4的si RNA(HDAC4si RNA)分别通过脂质体转染至细胞,应用实时荧光定量(q RT-PCR)检测细胞中mi R-140和HDAC4 m RNA表达情况,并采用蛋白质印迹法(WB)分析HDAC4蛋白水平。采用Transwell小室模型分析mi R-140上调和下调以及HDAC4调低对SGC-7901细胞迁移和侵袭能力的影响。结果 mi R-140转染可使HDAC4蛋白表达降低,HDAC4 m RNA水平则无明显变化。mi R-140上调与HDAC4调低均可显著抑制SGC-7901细胞的迁移和侵袭能力,而在转染了Anti-mi R-140的SGC-7901细胞中HDAC4蛋白表达增高,细胞迁移和侵袭能力增强。结论mi R-140在转录后水平调控HDAC4表达。mi R-140抑制胃癌细胞迁移和侵袭能力,部分是通过下调HDAC4而实现。mi R-140可能作为肿瘤转移诊断及治疗的新靶点。Objective To investigate the role of microRNA-140 （miR-140） in the migration and invasion potential of gastric cancer （GC）cell and the underlying mechanism. Method miR-140 mimics （miR-140）, miR-140 specific inhibitor （anti-miR-140） or siRNA against HDAC4 （HDAC4 siRNA） were transfected into human GC cell line SGC-7901 respectively using liposome, qRT-PCR was used to measure the expression levels of miR-140 and HDAC4 mRNA. HDAC4 protein was analyzed by Western blot. The in-vitro cell migration and invasion potential was determined by Transwell cham- ber assays after up-regulating or down-regulating miR-140 or knocking down HDAC4. Result The protein expression of HDAC4 was suppressed by miR-140 transfection without altering the target mRNA transcription level. The up-regula- tion of miR-140, andknock-down of HDAC4 by siRNA both inhibited the migration and invasion potential of SGC-7901 cells,down-regulation of miR-140 by the transfection of anti-miR-140 decreased the expression of HDAC4 protein, and enhanced the migration and invasion potential of SGC-7901 cells. Conclusion miR-140 directly targets HDAC4 in the transcriptional level, miR-140 suppresses the migration and invasion potential of GC cell, at least partly through the down- regulation of HDAC4. The findings of this study suggest that miR-140 may have a unique potential as a novel biomarker candidate for diagnosis and treatmentin tumor metastasis.

关 键 词：胃癌 microRNA-140 HDAC4 肿瘤迁移 肿瘤侵袭 

分 类 号：R735.2[医药卫生—肿瘤]