miR-1247 is Correlated with Prognosis of Pancreatic Cancer and Inhibits Cell Proliferation by Targeting Neuropilins
miR-1247 is Correlated with Prognosis of Pancreatic Cancer and Inhibits Cell Proliferation by Targeting Neuropilins
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miR-1247 与胰腺癌的预后相关，并通过靶向神经毡蛋白抑制细胞增殖。
DOI：
10.2174/1566524014666140228120014
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发表时间：
2014-03-01
影响因子：
2.5
通讯作者：
Yu, X.
中科院分区：
文献类型：
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作者：
Shi, S.;Lu, Y.;Yu, X.
越来越多的证据表明，microRNAs（miRNAs）在肿瘤的发生和发展中发挥重要作用，在肿瘤生物标志物和治疗药物方面具有巨大的潜力。miR-1247的异常表达已在几种癌症中被发现，并且通过miRNA调控网络分析预测其在胰腺癌的病理过程中起重要作用。我们通过原位杂交研究了miR-1247在胰腺癌组织芯片中的表达谱，发现miR-1247在胰腺癌组织中的表达与匹配的良性组织相比显著下调。高水平的miR-1247表达与胰腺癌患者较高的总生存期和无复发生存期呈正相关，而与肿瘤分级呈负相关。使用体外和体内模型，我们证明了miR-1247表达的增加抑制胰腺癌细胞的增殖、致瘤性、集落形成并触发G 0/G1细胞周期停滞。此外，我们通过western blot和荧光素酶报告基因分析证实了neuropilin 1（NRP 1）和neuropilin 2（NRP 2）是miR-1247的直接靶点。进一步的研究表明，低剂量全反式维甲酸（ATRA）可诱导胰腺癌细胞再分化，使miR-1247恢复。这些发现表明，新型肿瘤抑制因子miR-1247可以作为胰腺癌的潜在生物标志物和治疗剂。
Accumulating evidence indicates that microRNAs (miRNAs) have great potential as tumor biomarkers and therapeutic agents owing to their functions in tumorigenesis and cancer progression. Aberrant expression of miR-1247 has been found in several cancers and is predicted to play an important role in the pathological processes of pancreatic cancer by miRNA-regulated network analysis. We investigated the expression profile of miR-1247 in pancreatic cancer tissue microarray by in situ hybridization and found that miR-1247 was significantly down-regulated in pancreatic cancer tissues compared to matched benign tissues. High levels of miR-1247 expression were positively correlated with higher overall and recurrence free survival in pancreatic cancer patients, while negatively correlated with tumor grade. Using in vitro and in vivo models, we demonstrated that increased expression of miR-1247 inhibited proliferation, tumorigenicity, colony formation and triggered G0/G1 cell cycle arrest in pancreatic cancer cells. Moreover, we confirmed that neuropilin1 (NRP1) and neuropilin2 (NRP2) are direct targets of miR-1247 by western blot and luciferase reporter assay. Further studies indicated that low dose all trans retinoic acid (ATRA) can induce redifferentiation and restoration of miR-1247 in pancreatic cancer cells. These findings suggest that miR-1247, a novel tumor suppressor, can act as a potential biomarker and therapeutic agent for pancreatic cancer.