MicroRNA drop in the bloodstream and microRNA boost in the tumour caused by treatment with ribonuclease A leads to an attenuation of tumour malignancy.
MicroRNA drop in the bloodstream and microRNA boost in the tumour caused by treatment with ribonuclease A leads to an attenuation of tumour malignancy.
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DOI：
10.1371/journal.pone.0083482
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zenkova M
中科院分区：
文献类型：
--
作者：
Mironova N;Patutina O;Brenner E;Kurilshikov A;Vlassov V;Zenkova M
新的数据显示microRNA在介导肿瘤进展中的重要作用，为细胞毒性核糖核酸酶的可能分子靶点开辟了新的领域。最近，胰腺核糖核酸酶A的抗肿瘤和抗转移活性被证明，并且在此，通过寡核苷酸连接和检测（SOLiD™）测序技术的高通量测序分析了用核糖核酸酶A治疗后患有刘易斯肺癌的小鼠的肿瘤和血液中的微RNA的全基因组谱。测序数据显示，RNase A治疗导致肿瘤组织中116种microRNA的增加，血流中137种microRNA的显着下降，这一点得到了qPCR的证实。肿瘤中的microRNA增强伴随着microRNA加工基因的过表达：RNASEN（Drosha），xpo 5，dicer 1和eif 2c 2（Ago 2）。RNase A的核糖核酸酶活性被证明对于microRNA合成和microRNA加工基因的表达两者的激活是至关重要的。在肿瘤组织中，RNase A引起oncomirs和肿瘤抑制microRNA的上调，包括let-7家族的microRNA，已知负调节肿瘤进展。我们的研究结果表明，由RNase A治疗引起的microRNA签名的改变导致肿瘤恶性程度的减弱。
Novel data showing an important role of microRNAs in mediating tumour progression opened a new field of possible molecular targets for cytotoxic ribonucleases. Recently, antitumour and antimetastatic activities of pancreatic ribonuclease A were demonstrated and here genome-wide profiles of microRNAs in the tumour and blood of mice bearing Lewis lung carcinoma after treatment with RNase A were analysed by high-throughput Sequencing by Oligonucleotide Ligation and Detection (SOLiD™) sequencing technology. Sequencing data showed that RNase A therapy resulted in the boost of 116 microRNAs in tumour tissue and a significant drop of 137 microRNAs in the bloodstream that were confirmed by qPCR. The microRNA boost in the tumour was accompanied by the overexpression of microRNA processing genes: RNASEN (Drosha), xpo5, dicer1, and eif2c2 (Ago2). Ribonuclease activity of RNase A was shown to be crucial for the activation of both microRNA synthesis and expression of the microRNA processing genes. In the tumour tissue, RNase A caused the upregulation of both oncomirs and tumour-suppressor microRNAs, including microRNAs of the let-7 family, known to negatively regulate tumour progression. Our results suggest that the alteration of microRNA signature caused by RNase A treatment leads to the attenuation of tumour malignancy.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
8
作者：
Goparaju, C. M.;Blasberg, J. D.;Volinia, S.;Palatini, J.;Ivanov, S.;Donington, J. S.;Croce, C.;Carbone, M.;Yang, H.;Pass, H. I.
通讯作者：
Pass, H. I.
影响因子：
5.7
作者：
Karube, Y;Tanaka, H;Takahashi, T
通讯作者：
Takahashi, T
影响因子：
7.8
作者：
Choi SE;Fu T;Seok S;Kim DH;Yu E;Lee KW;Kang Y;Li X;Kemper B;Kemper JK
通讯作者：
Kemper JK