miR-328-3p mediates the anti-tumor effect in osteosarcoma via directly targeting MMP-16
miR-328-3p mediates the anti-tumor effect in osteosarcoma via directly targeting MMP-16
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DOI：
10.1186/s12935-019-0829-7
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发表时间：
2019-04-23
影响因子：
5.8
通讯作者：
Wang, Yansong
中科院分区：
文献类型：
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作者：
Shi, Jianhui;An, Gang;Wang, Yansong
背景越来越多的研究表明，microRNAs(MiRNAs)的异常表达导致多种肿瘤的进展。以往的研究表明miR-328-3p在不同类型的肿瘤中表达异常。然而，miR-328-3p在骨肉瘤中的作用及其机制尚不清楚。方法采用qRT-PCR方法检测miR-328-3p在骨肉瘤组织和骨肉瘤细胞系中的表达。用四甲基偶氮唑盐比色法分析miR-328-3p对细胞增殖的影响。采用集落形成实验和原位末端标记法分别检测OS细胞的增殖和凋亡。通过创伤愈合实验和小鼠体内移植实验检测OS细胞的迁移和成瘤能力。结果miR-328-3p在OS组织和细胞系中的表达显著降低。此外，过表达miR-328-3p抑制了OS细胞的增殖和迁移，但促进了OS细胞的凋亡。体内分析表明，miR-328-3P能有效抑制肿瘤的形成。根据蛋白质印迹分析和荧光素酶报告实验的结果，我们确定基质金属蛋白酶-16(MMP16)是miR-328-3p的直接靶标。结论miR-328-3p通过直接抑制MMP16的表达，抑制OS细胞的增殖、迁移，促进细胞凋亡，参与多种肿瘤的发生发展。MiR-328-3p/MMP16轴可能是OS发生发展的机制之一，为临床治疗OS提供了一种新的方法。
BackgroundIncreasing reports demonstrated that dysregulated expression of microRNAs (miRNAs) leads to the progression of various tumors. Previous studies revealed that miR-328-3p exhibited dysregulated expression in various types of tumors. However, its function and underlying mechanism in osteosarcoma (OS) are still unexplored.MethodsThe expression of miR-328-3p in the tissues and OS cell lines was detected by qRT-PCR analysis. The effects of miR-328-3p in the proliferation were analyzed by MTT assay. The proliferation and apoptosis of OS cells were examined by colony formation assay and TUNEL staining respectively. The migration and tumor formation ability of OS cells were measured by wound healing assay and xenograft in vivo mice assay. Furthermore, the regulatory roles of miR-328-3p/MMP16 were determined by western blot and luciferase reporter assay.ResultsThe expression of miR-328-3p was significantly decreased in OS tissues and cell lines. Furthermore, overexpression of miR-328-3p inhibited the cell proliferation and migration, but promoted the apoptosis of OS cells in vitro. Moreover, the analysis in vivo showed that miR-328-3p effectively suppressed the formation of tumors. According to the results of western blot analysis and luciferase reporter assay, we identified matrix metalloproteinase-16 (MMP-16) acted as a direct target of miR-328-3p. Moreover, the expression level of MMP-16, which participates in the occurrence and development of many cancers, was negatively correlated with the miR-328-3p expression in OS cells.ConclusionmiR-328-3p inhibited the proliferation, migration but accelerated the apoptosis of OS by directly inhibiting MMP-16. And miR-328-3p/MMP-16 axis may be one of the mechanisms of OS development and a novel potential method for the treatment of OS in clinic.