Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cancer Biol Ther. 2010 Oct 15;10(8):748-57. doi: 10.4161/cbt.10.8.13083.
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.
miR-17-5p 在胰腺癌中高表达,且与预后不良相关
微 RNA-17-92 簇是人类 B 细胞淋巴瘤和肺癌的致癌基因。先前的 microRNA 微阵列数据显示,miR-17-5p 是 miR-17-92 簇的成员,在胰腺癌中上调。然而,miR-17-5p 表达在胰腺癌发生中的作用尚未得到很好的研究。在本研究中,我们通过 qRT-PCR 测量了胰腺癌细胞系、原代培养的正常人胰腺导管细胞、80 例接受胰腺癌胰切除术的患者的福尔马林固定石蜡包埋(FFPE)组织样本和微切割细胞(包括正常导管上皮、胰腺上皮内瘤变 1B 和侵袭性导管癌细胞)中的 miR-17-5p 表达水平。此外,我们研究了上调 miR-17-5p 表达对胰腺癌细胞增殖和侵袭的影响。我们发现,与原代培养的正常导管细胞相比,胰腺癌细胞表达更高水平的 miR-17-5p。在 FFPE 和微切割样本中,miR-17-5p 在胰腺癌中也过表达。此外,对大切割 FFPE 样本的分析表明,高 miR-17-5p 表达与不良预后相关(p=0.03)。此外,体外实验表明,用 miR-17-5p 前体转染的 SUIT-2 和 KP-2 胰腺癌细胞与相应的对照细胞相比,细胞生长比率显著更高(p<0.001 和 p=0.012),侵袭细胞数量也显著更多(两者均 p<0.0001)。这些发现表明,miR-17-5p 在胰腺癌发生和癌症进展中发挥重要作用,并与胰腺癌预后不良相关。