MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4

// Xiang Xia 1,* , Kundong Zhang 1 , Gang Cen 1 , Tao Jiang 1 , Jun Cao 1 , Kejian Huang 1 , Chen Huang 1,* , Qian Zhao 2 and Zhengjun Qiu 1 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 Correspondence to: 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 Abstract 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 .