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首页> 外文期刊>Молекулярная биология >THE microRNA-29 PLAYS A CENTRAL ROLE IN OSTEOSARCOMA PATHOGENESIS AND PROGRESSION
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THE microRNA-29 PLAYS A CENTRAL ROLE IN OSTEOSARCOMA PATHOGENESIS AND PROGRESSION

机译：microRNA-29在骨肉瘤的发生和发展中起着中心作用

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摘要

Osteosarcoma is the most common type of bone cancer, with a peak incidence in the early childhood. The relationship between microRNAs (miRNAs) and cancer development attracted more and more attention over the last few years. Members of the miRNA-29 family, including miRNA-29a, miRNA-29b, and miRNA-29c were shown to participate in the development of rhabdomyosarcoma and hepatocarcinogenesis. Here, it has been demonstrated miRNA-29a and miRNA-29b expression levels to be downregulated in most of the osteosarcoma tissues (23 from 30). Besides, miRNA-29a displayed ability to induce apoptosis in both U20S and SAOS-2 osteoblastic cells. While miRNA-29 members induced apoptosis throughp53 gene activation, the effect of miR-NA-29a on osteoblastic cells was independent onp53 expression level. Moreover, Bcl-2 and Mcl-1 were earlier demonstrated to be the direct targets of miRNA-29 in many types of cancer tissues and cancers. In both U20S and SAOS-2 osteoblastic cell types, overexpression of miRNA-29a also downregulated Bcl-2 and Mcl-1, while silencing of miRNA-29a increased their expression. In addition, enhanced expression of miRNA-29a increased the expression of two tumor suppressor genes, E2F1 and E2F3. In summary, data obtained highlight the role of miRNA-29a in the regulation of osteoblastic cell apoptosis by silencing Bcl-2 and Mcl-1 and inducing E2F1 and E2F3 expression.
机译：骨肉瘤是最常见的骨癌类型，在儿童早期发病率最高。在过去的几年中，microRNA（miRNA）与癌症发展之间的关系越来越受到关注。已显示miRNA-29家族的成员，包括miRNA-29a，miRNA-29b和miRNA-29c参与横纹肌肉瘤的发展和肝癌的发生。在这里，已经证明miRNA-29a和miRNA-29b的表达水平在大多数骨肉瘤组织中均被下调（从30上升为23）。此外，miRNA-29a在U20S和SAOS-2成骨细胞中均具有诱导凋亡的能力。 miRNA-29成员通过p53基因激活诱导凋亡，而miR-NA-29a对成骨细胞的作用与onp53表达水平无关。而且，在许多类型的癌组织和癌症中，早先证明Bcl-2和Mcl-1是miRNA-29的直接靶标。在U20S和SAOS-2成骨细胞类型中，miRNA-29a的过表达也下调了Bcl-2和Mcl-1，而miRNA-29a的沉默则增加了它们的表达。此外，miRNA-29a的增强表达增加了两个抑癌基因E2F1和E2F3的表达。总之，获得的数据突出了miRNA-29a通过沉默Bcl-2和Mcl-1并诱导E2F1和E2F3表达在成骨细胞凋亡调控中的作用。

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