MicroRNA-106b promotes colorectal cancer cell migration and invasion by directly targeting DLC1.
MicroRNA-106b promotes colorectal cancer cell migration and invasion by directly targeting DLC1.
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DOI：
10.1186/s13046-015-0189-7
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发表时间：
2015-07-30
期刊：
影响因子：
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通讯作者：
Zhou T
中科院分区：
文献类型：
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作者：
Zhang GJ;Li JS;Zhou H;Xiao HX;Li Y;Zhou T
越来越多的证据表明，microRNAs （miRNAs）在肿瘤的发生、发展和转移中起着重要的作用。miR-106b的异常表达已在几种癌症中得到报道。然而，miR-106在结直肠癌（CRC）中的作用和潜在机制尚未得到解决。采用定量RT-PCR（qRT-PCR）评估CRC细胞系和患者标本中miR-106b的水平。MTT法检测细胞增殖，伤口愈合法和transwell法检测细胞迁移和侵袭能力。通过qRT-PCR、western blot和荧光素酶检测miR-106b的靶基因。miR-106b在转移性结直肠癌组织和细胞系中显著上调，且miR-106b的高表达与淋巴结转移和晚期临床分期相关。此外，miR-106b过表达增强，而miR-106b缺失减少CRC细胞的迁移和侵袭。此外，我们发现DLC1是miR-106b的直接靶点，揭示了其在CRC样本中的表达与miR-106b呈负相关，并表明其重新引入逆转了miR-106b诱导的CRC细胞迁移和侵袭。此外，生存分析显示，高mi-106b/低DLC1的患者总生存期（OS）和无病生存期（DFS）较短，证实miR-106b可能是结直肠癌患者OS和DFS的独立预后因素。我们的研究结果表明，miR-106b通过靶向DLC1促进结直肠癌细胞的迁移和侵袭。该miRNA可能作为结直肠癌的潜在预后生物标志物和治疗靶点。
Growing evidence suggests that microRNAs (miRNAs) play an important role in tumor development, progression and metastasis. Aberrant miR-106b expression has been reported in several cancers. However, the role and underlying mechanism of miR-106 in colorectal cancer (CRC) have not been addressed. Quantitative RT-PCR(qRT-PCR) was performed to evaluate miR-106b levels in CRC cell lines and patient specimens. Cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing assay and transwell assay. The target gene of miR-106b was determined by qRT-PCR, western blot and luciferase assays. miR-106b was significantly up-regulated in metastatic CRC tissues and cell lines, and high miR-106b expression was associated with lymph node metastasis and advanced clinical stage. In addition, miR-106b overexpression enhances, whereas miR-106b depletion reduces CRC cell migration and invasion. Moreover, we identify DLC1 as a direct target of miR-106b, reveal its expression to be inversely correlated with miR-106b in CRC samples and show that its re-introduction reverses miR-106b-induced CRC cell migration and invasion. Furthermore, survival analyses showed the patients with high mi-106b/low DLC1 had shorter overall survival (OS) and disease-free survival (DFS) rates, and confirmed miR-106b may be an independent prognostic factor for OS and DFS in CRC patients. Our findings indicate that miR-106b promotes CRC cell migration and invasion by targeting DLC1. This miRNA may serve as a potential prognostic biomarker and therapeutic target for CRC.