Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy.
Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy.
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骨肉瘤中含有差异表达的 microRNA 和 mRNA 的外泌体可以预测化疗反应
DOI：
10.18632/oncotarget.18373
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发表时间：
2017-09-29
期刊：
影响因子：
--
通讯作者：
Fan SW
中科院分区：
文献类型：
--
作者：
Xu JF;Wang YP;Zhang SJ;Chen Y;Gu HF;Dou XF;Xia B;Bi Q;Fan SW
骨肉瘤（OS）的一个主要挑战是为个体患者选择最有效的化疗药物，而无效的化疗增加了患者的死亡率并降低了患者的生活质量。这强调了需要评估每个患者对每种化疗剂应答的概率。我们开发了一种针对具有不同化疗反应的OS患者的血清外泌体microRNA和mRNA的分析策略。化疗反应差的OS患者与化疗反应好的OS患者相比，有12个miRNAs表达上调，18个miRNAs表达下调，差异有统计学意义（p<0.05）。此外，miR-124、miR-133 a、miR-199 a-3 p和miR-385在具有独立OS队列的反应不良患者中得到验证并显著降低。而miR-135 b、miR-148 a、miR-27 a和miR-9在血清外泌体中显著过表达。DIANA-mirPath的生物信息学分析表明，癌症中的蛋白聚糖、Hippo信号通路、癌症中的通路、癌症中的转录失调、PI 3 K-Akt信号通路、Ras信号通路、泛素介导的蛋白水解、癌症中的胆碱代谢是最突出的富含分位数的通路，其miRNA模式与较差的化疗反应相关。不同化疗反应的OS患者exosomes中Annexin 2、Smad 2、MTAP、Cdc 42相互作用蛋白4、色素上皮衍生因子、WWOX、Cdc 5L、P27等mRNA的表达存在差异。这些数据表明，外泌体RNA分子是可靠的生物标志物在不同的化疗敏感性骨肉瘤分类。
A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0.05). In addition, miR-124, miR133a, miR-199a-3p, and miR-385 were validated and significantly reduced in poorly responded patients with an independent OS cohort. While miR-135b, miR-148a, miR-27a, and miR-9 were significantly over expressed in serum exosomes. Bioinformatic analysis by DIANA-mirPath demonstrated that Proteoglycans in cancer, Hippo signaling pathway, Pathways in cancer, Transcriptional misregulation in cancer, PI3K-Akt signaling pathway, Ras signaling pathway, Ubiquitin mediated proteolysis, Choline metabolism in cancer were the most prominent pathways enriched in quantiles with the miRNA patterns related to poor chemotherapeutic response. Messenger RNAs(mRNAs) includingAnnexin2, Smad2, Methylthioadenosine phosphorylase (MTAP), Cdc42-interacting protein 4 (CIP4), Pigment Epithelium-Derived Factor (PEDF), WW domain-containing oxidoreductase (WWOX), Cell division cycle 5-like (Cdc5L), P27 were differentially expressed in exosomes in OS patients with different chemotherapeutic response. These data demonstrated that exosomal RNA molecules are reliable biomarkers in classifying osteosarcoma with different chemotherapy sensitivity.
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影响因子：
11.2
作者：
Jones KB;Salah Z;Del Mare S;Galasso M;Gaudio E;Nuovo GJ;Lovat F;LeBlanc K;Palatini J;Randall RL;Volinia S;Stein GS;Croce CM;Lian JB;Aqeilan RI
通讯作者：
Aqeilan RI
影响因子：
--
作者：
Salah Z;Arafeh R;Maximov V;Galasso M;Khawaled S;Abou-Sharieha S;Volinia S;Jones KB;Croce CM;Aqeilan RI
通讯作者：
Aqeilan RI
影响因子：
7
作者：
Jansen, Flip H.;Krijgsveld, Jeroen;Jenster, Guido
通讯作者：
Jenster, Guido
影响因子：
4.3
作者：
Pei, Hong;Jin, Zhiliang;Guo, Weichun
通讯作者：
Guo, Weichun
影响因子：
45.3
作者：
Ramaswamy, S;Golub, TR
通讯作者：
Golub, TR