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微小 RNA miR-17-5p 在胰腺癌中过表达,与不良预后相关,并且参与癌细胞增殖和侵袭。

MicroRNA miR-17-5p is overexpressed in pancreatic cancer, associated with a poor prognosis, and involved in cancer cell proliferation and invasion.

机构信息

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Cancer Biol Ther. 2010 Oct 15;10(8):748-57. doi: 10.4161/cbt.10.8.13083.

Abstract

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.

摘要

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。

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