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鉴定 APRIL 敲低的结直肠癌细胞中的 microRNA 靶相互作用。

Identification of microRNA-target interaction in APRIL-knockdown colorectal cancer cells.

机构信息

Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, School of Public Health, Nantong University, Nantong, China.

出版信息

Cancer Gene Ther. 2011 Jul;18(7):500-9. doi: 10.1038/cgt.2011.19. Epub 2011 May 20.

Abstract

MicroRNAs (miRNAs) regulate mammalian gene expression by targeting mRNAs and have key roles in several cellular processes, including differentiation, development, apoptosis and cancer pathomechanisms. Our previous studies have confirmed that a proliferation-inducing ligand (APRIL) gene is overexpressed in colorectal cancer (CRC) tumors and SW480 cells. To study the potential mechanisms of APRIL gene in the occurrence and development of the CRC, herein, we investigated whether APRIL-knockdown had the inhibitory effect on the growth of SW480 cells and had the simultaneous expression changes of miRNAs and mRNAs by microarrays. Our results suggest that siRNA-APRIL can effectively inhibit the growth of SW480 cells in vitro and in vivo and several miRNAs via specific pathways might be involved in regulating the phenotype of loss-of-function in APRIL-knockdown SW480 cells. Thus, our study highlights the possible mechanisms of miRNA-target regulating the function of APRIL gene in CRC cells, moreover, siRNA-APRIL holds great promise as a novel gene therapy approach for APRIL- positive CRC treatment.

摘要

微小 RNA(miRNAs)通过靶向 mRNAs 来调节哺乳动物基因表达,在包括分化、发育、凋亡和癌症发病机制在内的几种细胞过程中具有关键作用。我们之前的研究证实,增殖诱导配体(APRIL)基因在结直肠癌(CRC)肿瘤和 SW480 细胞中过表达。为了研究 APRIL 基因在 CRC 发生和发展中的潜在机制,在此,我们通过微阵列研究了 APRIL 敲低对 SW480 细胞生长的抑制作用以及同时发生的 miRNAs 和 mRNAs 的表达变化。我们的结果表明,siRNA-APRIL 可以有效地抑制 SW480 细胞在体外和体内的生长,并且可能通过特定途径涉及几种 miRNAs 来调节 APRIL 敲低 SW480 细胞中功能丧失的表型。因此,我们的研究强调了 miRNA 靶向调节 CRC 细胞中 APRIL 基因功能的可能机制,此外,siRNA-APRIL 作为 APRIL 阳性 CRC 治疗的新型基因治疗方法具有很大的潜力。

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