MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis.
MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis.
复制标题
MiR-497 下调导致胰腺癌恶性并与不良预后相关
DOI：
10.18632/oncotarget.2184
复制
发表时间：
2014-08-30
期刊：
影响因子：
--
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Xu J;Wang T;Cao Z;Huang H;Li J;Liu W;Liu S;You L;Zhou L;Zhang T;Zhao Y
化疗耐药是胰腺癌患者预后不良的原因之一。然而，耐药机制仍不清楚。在这里，我们筛选了与胰腺癌耐药相关的miRNAs，并鉴定了一组在吉西他滨耐药的胰腺癌细胞中表达异常的miRNAs，包括13个下调的miRNAs和20个上调的miRNAs。对miR-497的进一步研究表明，miR-497抑制细胞增殖，减少S期细胞的比例，使细胞对吉西他滨和厄洛替尼重新增敏，并减弱迁移和侵袭能力。此外，成纤维细胞生长因子2和成纤维细胞生长因子受体1被确认为miR-497靶点。体内过表达miR-497抑制肿瘤生长。此外，miR497在胰腺癌组织中的表达显著低于癌旁组织(P=0.000)。MiR497低表达是胰腺癌预后不良的独立危险因素(P=2.762，95%可信区间：1.159~6.579)。提示miR-497可能成为胰腺癌新的治疗靶点和预后标记物。
Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159–6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer.