MicroRNA-377 predicts poor clinical outcome of gastric cancer and induces tumorigenesis by targeting multiple tumor-suppressor genes
MicroRNA-377 predicts poor clinical outcome of gastric cancer and induces tumorigenesis by targeting multiple tumor-suppressor genes
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DOI：
10.3892/or.2015.3981
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发表时间：
2015-07-01
期刊：
影响因子：
4.2
通讯作者：
Tang, Jin-Hai
中科院分区：
文献类型：
--
作者：
Wen, Xu;Wu, Jian-Qiu;Tang, Jin-Hai
胃癌（GC）是世界范围内癌症死亡的主要原因。MicroRNA是一类进化上保守的非编码小RNA，对基因表达的调控至关重要。microRNA（miRNA）的异常表达与肿瘤的发生和预后有关。在本研究中，使用RT-qPCR和MTT法评估miR-377的临床意义。结果显示，miR-377在胃癌组织中的表达较正常胃组织上调，在胃癌细胞系中的表达水平较正常胃细胞增高。此外，miR-377表达与临床病理特征，特别是远处转移、TNM分期和早期复发之间存在显著相关性。与miR-377表达较低的胃癌患者相比，miR-377表达较高的胃癌患者的总体生存率（OR）显著较差，复发时间较短。考克斯回归分析确定miR-377过表达为GC的独立预后因素。miR-377在MKN-45 GC细胞中的过表达显著促进细胞增殖，而miR-377的抑制抑制了这些作用。此外，miR-377通过直接靶向这些靶基因的3 '非翻译区下调p53、PTEN和TIMP 1的表达。总之，miR-377有可能成为胃癌发生和预后的一个新的分子预测生物标志物，对胃癌的靶向治疗和预后判断有一定的指导意义。
Gastric cancer (GC) is a major cause of cancer mortality worldwide. MicroRNAs are evolutionally conserved small non-coding RNAs that are critical for the regulation of gene expression. The aberrant expression of microRNA (miRNA) is involved in tumorigenesis and prognosis. In the present study, the clinical significance of miR-377 was assessed using RT-qPCR and MTT assay. The results showed that the expression of miR-377 was upregulated in GC compared with normal gastric tissues, and its expression level was increased in GC cell lines compared with normal gastric cells. In addition, there was a significant association between miR-377 expression and clinicopathological characteristics, in particular distant metastasis, TNM stage and early recurrence. GC patients with a higher miR-377 expression showed significantly poorer overall survival (OR) and shorter time to recurrence than those with a lower miR-377 expression. The Cox regression analysis identified miR-377 overexpression as an independent prognostic factor for GC. Overexpression of miR-377 in MKN-45 GC cells significantly promoted cell proliferation, whereas the suppression of miR-377 inhibited these effects. Furthermore, miR-377 downregulated p53, PTEN and TIMP1 expression by directly targeting the 3'-untranslated region of these target genes. Collectively, miR-377 potentially served as a new molecular predictive biomarker of GC tumorigenesis and prognosis, which may be useful in targeted therapy and the prognosis of GC patients.