MiR-32 promotes tumorigenesis of colorectal cancer by targeting BMP5
MiR-32 promotes tumorigenesis of colorectal cancer by targeting BMP5
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DOI：
10.1016/j.biopha.2018.07.050
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发表时间：
2018-10-01
影响因子：
7.5
通讯作者：
Yang, Jin
中科院分区：
文献类型：
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作者：
Chen, Erfei;Li, Qiqi;Yang, Jin
MiRNA调控是表观遗传变化的重要途径。Mir-32作为一种致癌基因已在多项研究中被报道，然而，其在结直肠癌（CRC）中的作用和靶点尚不清楚。在这项研究中，我们旨在通过生物信息学分析和功能分析探讨miR-32在结直肠癌中的作用。我们收集了28对结直肠癌肿瘤组织和邻近正常组织，证实miR-32在结直肠癌中显著上调。来自癌症基因组图谱（TCGA）的表达和临床数据发现，miR-32的表达与结直肠癌淋巴浸润、转移有关，并与患者的不良生存率相关。功能研究表明，在LoVo细胞中过表达miR-32可促进细胞增殖和迁移，而在HCT 116细胞中抑制miR-32则显示相反的结果。利用生物信息学，我们发现骨形态发生蛋白5 （Bone morphogenetic protein 5, BMP5）是miR-32的直接靶点，肿瘤抑制因子BMP5的缺失可能部分归因于miR-32的失调。miR-32与BMP5在结直肠癌中呈负相关，尤其是在晚期肿瘤患者中。此外，在LoVo细胞中共转染miR-32模拟物和BMP5重组载体表明，BMP5可以逆转miR-32的肿瘤效应。综上所述，我们的研究结果表明miR-32/BMP5轴在CRC肿瘤发生中起着重要作用。
MiRNA regulation is a crucial way of epigenetic changes. Mir-32 has been reported in several studies as an oncogene, however, its role and target in colorectal cancer (CRC) remains unclear. In this study, we aimed to explore the role of miR-32 in CRC using bioinformatic analysis and functional assays. We collected 28 pairs of CRC tumor tissues and adjacent normal tissues and confirmed miR-32 was significantly upregulated in CRC. Expression and clinical data from The Cancer Genome Atlas (TCGA) identified miR-32 expression is associated with CRC lymphatic invasion, metastasis, and correlates with patients' poor survival. Functional studies demonstrated that overexpression of miR-32 in LoVo cells promoted cell proliferation and migration, whereas inhibition of miR-32 in HCT 116 cells showed the opposite results. Using bioinformatics, we identified Bone morphogenetic protein 5 (BMP5) is a direct target of miR-32, and loss of tumor suppressor BMP5 may partially due to the miR-32 dysregulation. The inverse correlation between miR-32 and BMP5 was observed in CRC, especially in advanced tumor patients. Moreover, cotransfection of miR-32 mimics and BMP5 recombinant vector in LoVo cells demonstrated that BMP5 could reverse the oncomir effect of miR-32. Taken together, our results suggested a significant role of miR-32/BMP5 axis in CRC tumorigenesis.