Abstract

Pancreatic cancer (PC), as the leading cause of cancer death worldwide, is one of the deadliest tumors with a very low 5-year survival rate. Therefore, it is urgent to seek new biomarkers of PC for more accurate and reliable treatments. To identify the differentially expressed miRNAs (DEM) in PC tissues, we performed the systematic microarray and qRT-PCR analyses. We found miR-196b was the top dysregulated DEM in PC tissues as compared with the corresponding adjacent tissues, and positively correlated with poor differentiation, tumor size, lymphatic invasion and TNM stage. Furthermore, the late apoptosis rate was significantly reduced, while the cell proliferation was increased in PANC-1 and ASPC-1 cell-lines after treatment with miR-196b mimics. The qRT-PCR and Western blot analysis demonstrated that the level of CADM1 in PANC-1 cells response to the alteration of miR-196b. Moreover, blockade of CADM1 could decrease the late apoptosis in PANC-1 cells as up-regulated by inhibition of miR-196b. Finally, luciferase report assay confirmed that CADM1 was the direct target gene of miR-196b. Overexpression of miR-196b in PC tissues can increase the late apoptosis of pancreatic cancer cells by targeting CADM1. These findings suggested miR-196b is a potential target for diagnosis and therapeutics of human pancreatic cancer.

Highlights

  • Pancreatic cancer (PC), the 7th leading cause of cancer death worldwide, is one of the deadliest tumors with a very low 5-year survival rate[1, 2]

  • To find out candidate miRNAs associated with PC, 20 paired pancreatic cancer tissues and adjacent tissues were collected during resections, and were assessed by NanoString nCounter Human miRNA assay

  • Pancreatic cancer tissues and adjacent tissues was examined by Principal Component Analysis (PCA), and the 3-dimensional PCA (3d-PCA) plot showed that the expression profiles of miRNAs clustered into two separate groups, which was consistent with the source of tissues (Fig. 1A)

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Summary

Introduction

Pancreatic cancer (PC), the 7th leading cause of cancer death worldwide, is one of the deadliest tumors with a very low 5-year survival rate (ranges from 2% to 9%)[1, 2]. Several studies have reported many miRNAs (e.g., miR-21, miR-25, miR-155, and miR-210) were dysregulated in PC, but the clinical value and the exact role in pathogenesis of PC were still not clear[14, 15]. Systematically identifying differentially expressed miRNAs, to account for the pathogenesis of PC and be associated with clinical characteristics of PC, will provide more evidence for the diagnosis and treatment of PC. We identified the differentially expressed miRNAs in PC tissues, find out the correlation of these miRNAs with characteristics of PC patients, and investigated the role of miR-196b in regulating apoptosis and proliferation in PANC-1 and ASPC-1 cells. Our results indicated miR-196b is a potential target to diagnosis and therapeutics of pancreatic cancer

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