miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway
miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway
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DOI：
10.1007/s13277-012-0446-8
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Sun, Weijia
中科院分区：
文献类型：
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作者：
Hu, Yongjun;Ou, Yanglu;Sun, Weijia
胰腺癌的特点是早期转移和高死亡率。在这项研究中，miR-143在胰腺癌细胞中的侵袭和转移中的作用进行了研究。通过腺病毒携带的miR-143表达盒建立miR-143表达。采用RT-PCR和Western blot方法分别检测基因的mRNA和蛋白表达水平。Rho GTPases活性通过下拉测定来测量。在体外测试miR-143在Panc-1细胞的迁移和侵袭中的作用。在肝转移模型中测试miR-143的抗转移作用，而在异种移植Panc-1肿瘤模型中测试其抗肿瘤生长作用。结果表明，ARHGEF 1（GEF 1）、ARHGEF 2（GEF 2）和K-RAS基因是miR-143的靶基因。miR-143表达显著降低GEF 1、GEF 2和K-RAS基因的mRNA和蛋白水平;降低RhoA、Rac 1和Cdc 42 GTP酶的组成性活性;降低MMP-2和MMP-9的蛋白水平;但显著增加E-cadherin的蛋白水平。miR-143表达还显着抑制Panc-1细胞的体外迁移和侵袭、肝转移和体内异种移植肿瘤生长。我们的研究表明，miR-143在胰腺癌的侵袭和转移中起着重要作用，miR-143是胰腺癌治疗的潜在靶点。
Pancreatic cancer is characterized by early metastasis and high mortality. In this study, the role of miR-143 in invasion and metastasis was investigated in pancreatic cancer cells. miR-143 expression was established by an adenovirus-carried miR-143 expression cassette. mRNA and protein levels of gene expression were examined by RT-PCR and Western blot assay, respectively. Rho GTPases activity was measured by the pull down assay. The role of miR-143 in migration and invasion of Panc-1 cells was tested in vitro. The antimetastatic effect of miR-143 was tested in a liver metastasis model, while its antitumor growth effect was tested in a xenograft Panc-1 tumor model. Results demonstrated that ARHGEF1 (GEF1), ARHGEF2 (GEF2), and K-RAS genes are the targets of miR-143. miR-143 expression significantly decreased mRNA and protein levels of GEF1, GEF2, and K-RAS genes; lowered the constitutive activities of RhoA, Rac1, and Cdc42 GTPases; decreased the protein levels of MMP-2 and MMP-9; but significantly increased the protein level of E-cadherin. miR-143 expression also significantly inhibited the migration and invasion of Panc-1 cells in vitro, liver metastasis, and xenograft tumor growth in vivo. Our study suggested that miR-143 plays a central role in the invasion and metastasis of pancreatic cancer and miR-143 is a potential target for pancreatic cancer therapy.