Abstract
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. 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. 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. MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4.
Highlights
Pancreatic ductal adenocarcinoma(PDAC) is one of the most notorious cancers, with an overall 5-year survival rate of less than 5% and a median survival time of approximate 6 months [1]
MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4
Since miR-301a-3p expression level was positively correlated to pathological features, we postulated that deregulation of miR-301a-3p may pose a promoting impact on PDAC progression and function as a predictor for poor prognosis
Summary
Pancreatic ductal adenocarcinoma(PDAC) is one of the most notorious cancers, with an overall 5-year survival rate of less than 5% and a median survival time of approximate 6 months [1]. Curative resection is the core of successful therapy to PDAC patients [2], but only 10%-15% of them are diagnosed at the early stages when surgical resection can be offered [3]. PDAC still refers to the lowest patient survival rate among any solid cancers [6]. Speaking, this dismal outcome is attributed to the aggressive local invasion, early metastasis and dissemination of the PDAC cells [7]. Aim to determine the clinicopathological and prognostic role of miR301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo
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