MicroRNA miR-17-5p is overexpressed in pancreatic cancer, associated with a poor prognosis and involved in cancer cell proliferation and invasion
MicroRNA miR-17-5p is overexpressed in pancreatic cancer, associated with a poor prognosis and involved in cancer cell proliferation and invasion
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DOI：
10.4161/cbt.10.8.13083
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发表时间：
2010-10-15
影响因子：
3.6
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
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作者：
Yu, Jun;Ohuchida, Kenoki;Tanaka, Masao
MicroRNA-17-92簇是人类B细胞淋巴瘤和肺癌的癌基因。以往的microRNA微阵列数据显示，miR-17-5p是miR-17-92簇的成员之一，在胰腺癌中表达上调。然而，miR-17-5p的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，我们用qRT-PCR方法检测了胰腺癌细胞系、原代培养的正常人胰腺导管细胞、80例胰腺癌切除患者的福尔马林固定石蜡包埋(FFPE)组织和显微解剖细胞(包括正常导管上皮细胞、胰腺上皮内瘤变-1B细胞和浸润性导管癌细胞)中miR-17-5p的表达水平。此外，我们还研究了miR-17-5p表达上调对胰腺癌细胞增殖和侵袭的影响。我们发现胰腺癌细胞较原代培养的正常导管细胞表达更高水平的miR-17-5p。MIR-17-5p在FFPE和显微解剖标本中也在胰腺癌组织中过表达。此外，大体解剖标本分析显示miR-17-5p高表达与预后不良相关(p=0.03)。此外，体外实验显示，转染miR-17-5P前体的Suit-2和KP-2胰腺癌细胞的细胞生长率显著高于相应的对照细胞(p<；0.001和p=0.012)，侵袭细胞数也显著增加(p<；0.0001)。提示miR-17-5p在胰腺癌的发生、发展中起重要作用，并与胰腺癌的预后不良有关。
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.