MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4
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Xiang Xia1,*, Kundong Zhang1, Gang Cen1, Tao Jiang1, Jun Cao1, Kejian Huang1, Chen Huang1,*, Qian Zhao2 and Zhengjun Qiu1
1 Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, China
2 Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis and National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai, China
* These authors have contributed equally to this work
Qian Zhao, email:
Zhengjun Qiu, email:
Keywords: miR-301a-3p; SMAD4; pancreatic ductal adenocarcinoma; xenograft tumor; prognosis
Received: February 10, 2015 Accepted: May 02, 2015 Published: May 12, 2015
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.
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