Guo Yong, Qi Yong, Guo Aitao, Du Chengxiong, Zhang Rong, Chu Xiaoyong
Department of Pathology, No. 161 Hospital of the People's Liberation Army, Wuhan, Hubei 430010, P.R. China.
Outpatient Department, The People's Liberation Army Naval University of Engineering, Wuhan, Hubei 430033, P.R. China.
Oncol Lett. 2017 Jun;13(6):4155-4160. doi: 10.3892/ol.2017.5964. Epub 2017 Mar 31.
Numerous aberrantly expressed microRNAs (miRNAs/miRs) have been identified in gastric cancer (GC); however, only a fraction of these have been functionally investigated and novel deregulated miRNAs in GC remain to be explored. Through examining two public miRNA expression profile datasets, the present study identified aberrantly expressed miRNAs in GC. One of these miRNA, miR-564, was identified to be downregulated in GC, which was validated in tissue samples from patients with GC by reverse transcription-quantitative polymerase chain reaction analysis. Targets of miR-564 were then predicted bioinformatically, including transcription factor E2F3 (E2F3), which was identified to be functionally enriched in several cancer signaling pathways. Furthermore, overexpression of miR-564 decreased the activity of a luciferase reporter carrying the 3'-untranslated region of E2F3, in addition to the mRNA and protein level of E2F3, indicating that miR-564 directly targets E2F3. These data suggest that by targeting E2F3, miR-564 may act as a tumor suppressor gene in gastric carcinogenesis.
在胃癌(GC)中已鉴定出许多异常表达的微小RNA(miRNA/miR);然而,其中只有一小部分进行了功能研究,GC中新型失调的miRNA仍有待探索。通过检查两个公开的miRNA表达谱数据集,本研究鉴定出GC中异常表达的miRNA。其中一种miRNA,即miR-564,被鉴定为在GC中下调,这通过逆转录-定量聚合酶链反应分析在GC患者的组织样本中得到验证。然后通过生物信息学预测miR-564的靶标,包括转录因子E2F3,该转录因子在几种癌症信号通路中功能富集。此外,miR-564的过表达降低了携带E2F3 3'-非翻译区的荧光素酶报告基因的活性,以及E2F3的mRNA和蛋白质水平,表明miR-564直接靶向E2F3。这些数据表明,通过靶向E2F3,miR-564可能在胃癌发生过程中作为肿瘤抑制基因发挥作用。