Ma Zhijun, Ma Yulan, Xia Qinghua, Li Yong, Li Ruidong, Chang Weilong, Chen Jinhuang, Leng Zhengwei, Tao Kaixiong
Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China.
Department of Cardiology, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Yinchuan, 750004, China.
J Cancer Res Clin Oncol. 2016 Jun;142(6):1201-12. doi: 10.1007/s00432-016-2139-y. Epub 2016 Mar 8.
MicroRNAs (miRs) have been frequently reported dysregulating in tumors and playing a crucial role in tumor development and progression. However, the expression of miR-155 and its role in gastric cancer (GC) are still obscure.
qRT-PCR was applied to detect miR-155 expression in 60 matched GC samples and four GC cell lines, and the relationship between miR-155 levels and clinicopathological features of GC was analyzed. Next, the effects of miR-155 on GC cell growth were evaluated by gain- and loss-of-function analysis. Finally, the target gene(s) of miR-155 in GC cells were explored.
Our results revealed that miR-155 levels were significantly lower in both GC tissues and GC cell lines than in their normal controls, and its expression inversely correlated with tumor size and the pathologic stage. Moreover, our study showed that enforced expression of miR-155 impaired GC cell proliferation, promoted G1 phase arrest and induced apoptosis in vitro. In addition, we identified cyclin D1 as the direct target of miR-155, and knockdown of cyclin D1 partially phenocopied the role of miR-155 in GC cells.
Our findings suggest that miR-155 may act as a potential diagnostic marker for early-stage GC and may represent a novel therapeutic target for GC treatment.
微小RNA(miRs)在肿瘤中经常被报道存在失调,并在肿瘤发生和发展中起关键作用。然而,miR-155在胃癌(GC)中的表达及其作用仍不清楚。
应用qRT-PCR检测60对匹配的GC样本和4种GC细胞系中miR-155的表达,并分析miR-155水平与GC临床病理特征之间的关系。接下来,通过功能获得和功能缺失分析评估miR-155对GC细胞生长的影响。最后,探索miR-155在GC细胞中的靶基因。
我们的结果显示,GC组织和GC细胞系中miR-155水平均显著低于其正常对照,且其表达与肿瘤大小和病理分期呈负相关。此外,我们的研究表明,miR-155的过表达在体外损害GC细胞增殖,促进G1期阻滞并诱导凋亡。此外,我们确定细胞周期蛋白D1是miR-155的直接靶标,敲低细胞周期蛋白D1部分模拟了miR-155在GC细胞中的作用。
我们的研究结果表明,miR-155可能作为早期GC的潜在诊断标志物,并可能代表GC治疗的新靶点。