MicroRNAmiR-17-5pis overexpressed in pancreatic cancer, associated with a poor prognosis, and involved in cancer cell proliferation and invasion

• DOI: 10.4161/cbt.10.8.13083
• Publication Date: 2010-11-22T21:57:36Z
• Authors: Jun Yu; Kenoki Ohuchida; Kazuhiro Mizumoto; Hayato Fujita; Kouhei Nakata; Masao Tanaka
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Paraffin Embedding; Tissue Fixation; Reverse Transcriptase Polymerase Chain Reaction; Middle Aged; Prognosis; Survival Analysis; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Multivariate Analysis; Humans; Female; Neoplasm Invasiveness; Aged; Cell Proliferation

The microRNA-17-92 cluster is an oncogene in human B cell lymphomas and lung cancers. Previous microRNA microarray data revealed that miR-17-5p, a member of the miR-17-92 cluster, is upregulated in pancreatic cancer. However, the involvement of miR-17-5p expression in pancreatic carcinogenesis has not well been studied. In the present study, we measured the miR-17-5p expression levels in pancreatic cancer cell lines, primary cultures of normal human pancreatic ductal cells, formalin-fixed paraffin-embedded (FFPE) tissue samples derived from 80 patients who underwent pancreatectomy for pancreatic cancer and microdissected cells (including normal ductal epithelial, pancreatic intraepithelial neoplasia-1B and invasive ductal carcinoma cells) by qRT-PCR. Furthermore, we investigated the effects of upregulation of miR-17-5p expression on the proliferation and invasion of pancreatic cancer cells. We found that pancreatic cancer cells expressed higher levels of miR-17-5p than primary cultured normal ductal cells. miR-17-5p was also overexpressed in pancreatic cancer in FFPE and microdissected samples. Furthermore, analysis of macrodissected FFPE samples revealed that high miR-17-5p expression was associated with a poor prognosis (p = 0.03). In addition, in vitro experiments revealed that SUIT-2 and KP-2 pancreatic cancer cells transfected with the miR-17-5p precursor showed significantly higher cell growth ratios than the corresponding control cells (p < 0.001 and p = 0.012, respectively), as well as significantly higher numbers of invading cells (p < 0.0001 for both). The present findings suggest that miR-17-5p plays important roles in pancreatic carcinogenesis and cancer progression, and is associated with a poor prognosis in pancreatic cancer.