MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4
MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4
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MicroRNA-301a-3p 通过 SMAD4 的负调节促进胰腺癌进展
DOI：
10.18632/oncotarget.4124
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发表时间：
2015-08-28
期刊：
影响因子：
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通讯作者：
Qiu, Zhengjun
中科院分区：
文献类型：
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作者：
Xia, Xiang;Zhang, Kundong;Qiu, Zhengjun
背景旨在确定miR-301a-3p在胰腺导管腺癌（PDAC）中的临床病理和预后作用，探讨miR-301a-3p的体外和体内生物学机制。方法通过组织芯片分析，研究PDAC患者中miR-301a-3p的表达及其临床病理相关性和预后意义。 qRT-PCR 用于测试 PDAC 组织和细胞系中 miR-301a-3p 的表达。进行了包括体外和体内的功能实验。结果 miR-301a-3p 在淋巴结转移和病理分期晚期的 PDAC 患者中表达显着升高，并被确定为生存较差的独立预后因素。在 PDAC 样本和细胞系中，与匹配的非肿瘤组织和正常胰腺导管细胞相比，miR-301a-3p 分别显着上调。 miR-301a-3p 的过表达增强了 PDAC 细胞的体外集落、侵袭和迁移能力以及体内致瘤性。此外，通过细胞和小鼠异种移植实验，SMAD4被鉴定为miR-301a-3p的靶基因。在 PDAC 组织微阵列中，在肿瘤和相应的非肿瘤组织中观察到 miR-301a-3p ISH 评分与 SMAD4 IHC 评分之间存在显着负相关。结论 MiR-301a-3p是PDAC中的一种新型致癌基因，其致癌活性可能与抑制靶基因SMAD4有关。
Background Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. Methods By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. Results Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues. Conclusion MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.