Wen Xu, Wu Jian-Qiu, Peng Wei, Feng Ji-Feng, Tang Jin-Hai
Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
Oncol Rep. 2015 Jul;34(1):203-10. doi: 10.3892/or.2015.3981. Epub 2015 May 15.
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.
胃癌（GC）是全球癌症死亡的主要原因。微小RNA是进化上保守的小非编码RNA，对基因表达的调控至关重要。微小RNA（miRNA）的异常表达与肿瘤发生和预后有关。在本研究中，使用逆转录定量聚合酶链反应（RT-qPCR）和MTT法评估了miR-377的临床意义。结果显示，与正常胃组织相比，miR-377在胃癌中表达上调，与正常胃细胞相比，其在胃癌细胞系中的表达水平升高。此外，miR-377表达与临床病理特征之间存在显著关联，特别是远处转移、TNM分期和早期复发。miR-377表达较高的胃癌患者总体生存率（OR）显著较低，复发时间比miR-377表达较低的患者短。Cox回归分析确定miR-377过表达是胃癌的独立预后因素。miR-377在MKN-45胃癌细胞中的过表达显著促进细胞增殖，而抑制miR-377则抑制这些作用。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TIMP1的表达。总的来说，miR-377可能作为胃癌发生和预后的一种新的分子预测生物标志物，这可能有助于胃癌患者的靶向治疗和预后评估。
