miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression.
miR-133b, a muscle-specific microRNA, is a novel prognostic marker that participates in the progression of human colorectal cancer via regulation of CXCR4 expression.
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DOI：
10.1186/1476-4598-12-164
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发表时间：
2013-12-13
期刊：
影响因子：
37.3
通讯作者：
Chen YQ
中科院分区：
文献类型：
--
作者：
Duan FT;Qian F;Fang K;Lin KY;Wang WT;Chen YQ
MicroRNA-133 b（miR-133 b）是一种肌肉特异性microRNA，据报道，与邻近的非肿瘤组织相比，在人结直肠癌（CRC）中下调。然而，其在CRC中的诊断价值和作用尚未被描述。CXC趋化因子受体4（CXCR 4）参与多种细胞过程，如细胞侵袭相关的信号通路，被预测为miR-133 b的潜在靶点。本研究的目的是探讨miR-133 b和CXCR 4在结直肠癌发生和侵袭中的相关性和功能。使用实时定量RT-PCR（qRT-PCR）检测来自CRC患者的31个肿瘤样品及其邻近非肿瘤组织以及6个CRC细胞系中成熟miR-133 b和CXCR 4表达水平。使用荧光素酶报告基因测定和Western印迹来验证CXCR 4作为miR-133 b的推定靶基因。使用qRT-PCR和Western印迹分析评估miR-133 b对CXCR 4表达的调节，并使用SW-480和SW-620 CRC细胞系在体外评估外源性miR-133 b和CXCR 4对细胞侵袭和迁移的影响。在93.55%的CRC组织中观察到miR-133 B的显著下调，并且miR-133 B的表达在转移性肿瘤（C和D期，通过改良的Dukes分期系统分层）中比在原发性肿瘤（A和B期）中低得多。相反，52.63%的CRC样本中CXCR 4蛋白表达显著增加，并且CRC中CXCR 4表达增加与晚期肿瘤分期相关。通过荧光素酶报告基因测定，CXCR 4显示为miR-133 b的直接靶点，并且miR-133 b模拟物的转染抑制SW-480和SW-620 CRC细胞的侵袭并刺激细胞凋亡。我们的研究表明，下调的miR-133 b通过负调节CXCR 4而促进CRC中细胞侵袭和迁移的增加。这些结果可能对大肠癌治疗靶点的开发具有重要意义。
MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion. Mature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines. A significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells. Our study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC.
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