MiR-139-5p suppresses osteosarcoma cell growth and invasion through regulating DNMT1
MiR-139-5p suppresses osteosarcoma cell growth and invasion through regulating DNMT1
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DOI：
10.1016/j.bbrc.2018.04.124
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发表时间：
2018-09-05
影响因子：
3.1
通讯作者：
Guo, Yu-Hua
中科院分区：
文献类型：
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作者：
Shi, Yong-Kang;Guo, Yu-Hua
背景：越来越多的证据表明差异表达的miRNAs在骨肉瘤的进展中起着至关重要的作用。miR-139- 5 p在各种癌症中降低。方法：采用qRT-PCR和western blot方法检测miR-139 - 5 p和DNA甲基转移酶-1（DNMT 1）mRNA在骨肉瘤组织和细胞中的表达。通过细胞迁移和侵袭试验以及蛋白质印迹分析，研究miR-139- 5 p和DNMT 1对骨肉瘤细胞迁移、侵袭和上皮-间质转化（EMT）的影响。采用荧光素酶报告基因分析和western blot检测miR-139- 5 p与DNMT 1的关系。结果：miR-139 - 5 p在骨肉瘤组织和细胞系中表达明显降低，在骨肉瘤细胞系中表达明显降低。miR-139- 5 p过表达抑制骨肉瘤细胞的生长、迁移和侵袭，而miR-139- 5 p缺失促进骨肉瘤细胞的增殖、迁移和侵袭。随后，我们表征了DNMT 1是miR-139- 5 p的直接靶点，其与DNMT 1的3 '-非翻译区相互作用。miR-139- 5 p下调DNMT 1蛋白表达水平。我们还发现DNMT 1在骨肉瘤组织中的表达增加，并且与miR-139- 5 p的表达呈负相关。结论：miR-139 - 5 p通过下调DNMT 1表达抑制骨肉瘤的生长，为揭示骨肉瘤生长的分子机制提供了新的思路。(C)2018由Elsevier Inc.出版
Background: Accumulating evidence has suggested the crucial roles of differentially expressed miRNAs in osteosarcoma progression. MiR-139-5p was decreased in various cancers. However, the role of miR-139-5p in the development of osteosarcoma and the underlying mechanism remain to be addressed.Methods: MiR-139-5p and DNA methyltransferase-1 (DNMT1) mRNA expressions in osteosarcoma tissues and cells were detected by qRT-PCR and western blot analysis. The effects of miR-139-5p and DNMT1 on osteosarcoma cell migration, invasion and epithelial-mesenchymal transition (EMT) were investigated through cell migration and invasion assays, and western blot analysis. The relationship between miR-139-5p and DNMT1 was explored using luciferase reporter analysis and western blot. A xenograft tumor model was employed to verify the effects of miR-139-5p on osteosarcoma.Results: We found that miR-139-5p was strikingly decreased in osteosarcoma tissues and cell lines. MiR-139-5p over-expression suppressed osteosarcoma cell growth, migration and invasion, while loss of miR-139-5p promoted osteosarcoma cell proliferation, migration and invasion. Following, we characterized that DNMT1 was a direct target of miR-139-5p that interacted with the 3'-untranslated region of DNMT1. MiR-139-5p regulated a down-regulation in DNMT1 protein expression levels. We also found that DNMT1 expression was increased and negatively correlated with miR-139-5p expression in osteosarcoma tissues clinically. Xenograft tumor analysis suggested that miR-139-5p over-expression reduced tumor growth in osteosarcoma in vivo through decreasing DNMT1 expressions.Conclusion: MiR-139-5p suppressed the osteosarcoma progression by reducing DNMT1, supplying new insight into the molecular mechanism uncovering osteosarcoma growth. (C) 2018 Published by Elsevier Inc.