MicroRNA-141 Regulates Smad Interacting Protein 1 (SIP1) and Inhibits Migration and Invasion of Colorectal Cancer Cells

MicroRNA-141 Regulates Smad Interacting Protein 1 (SIP1) and Inhibits Migration and Invasion of Colorectal Cancer Cells
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MicroRNA-141 调节 Smad 相互作用蛋白 1 (SIP1) 并抑制结直肠癌细胞的迁移和侵袭

DOI:
10.1007/s10620-009-1008-9
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发表时间:
2010-08-01
影响因子:
3.1
通讯作者:
Su, Lei
Su, Lei
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Minghua;Xia, MicroGene;Su, Lei

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结直肠癌(CRC)是世界上第三大常见癌症。尽管最近在诊断和治疗方面取得了进展,但晚期疾病患者的预后仍然很差。microRNA(miRNAs)是一类内源性的非编码小RNA分子,在转录后水平对基因表达起着重要的调控作用。为探讨miR-141在结直肠癌细胞迁移和侵袭中的作用,采用实时荧光定量RT-PCR和Western blotting方法检测miR-141和Smad相互作用蛋白1(SIP 1)在结直肠癌细胞中的表达。采用创伤愈合实验和Matrigel体外侵袭实验研究miR-141对大肠癌细胞迁移和侵袭的影响。通过双荧光素酶报告基因检测miR-141对SIP 1的调控作用,发现miR-141的表达水平与SIP 1蛋白表达水平呈负相关,并与结直肠癌细胞的迁移和侵袭能力呈负相关。SIP 1是miR-141的功能性靶点,miR-141通过调控SIP 1抑制CRC细胞的迁移和侵袭。miR-141和SIP 1可能是CRC治疗的候选靶点。
Colorectal cancer (CRC) is the third most common cancer in the world. Despite recent advances in diagnostics and treatment, prognosis for patients with advanced disease is still poor. microRNAs (miRNAs) are a class of endogenous, small noncoding RNA molecules which are crucial regulators of gene expression at the posttranscriptional level. miRNAs participate in many biological events and play an important role in various human diseases, including CRC.This study is to identify the role of miR-141 in migration and invasion of CRC cells.Expression of miR-141 and Smad interacting protein 1 (SIP1) were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. The effect of miR-141 on migration and invasion of CRC cells was investigated using wound healing assay and Matrigel invasion assay in vitro. The regulation effect of miR-141 on SIP1 was evaluated by dual-luciferase reporter assay.We demonstrated that miR-141 levels correlate inversely with SIP1 protein levels as well as cell migration and invasion of CRC cells. SIP1 was identified as a functional target of miR-141.miR-141 regulates SIP1 to inhibit migration and invasion of CRC cells. miR-141 and SIP1 might be candidate therapeutic targets in CRC.