Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia.
Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia.
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microRNA-210对小儿急性淋巴细胞白血病预后及化疗药物反应的影响
DOI：
10.1111/cas.12370
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发表时间：
2014-04
期刊：
影响因子：
5.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Mei Y;Gao C;Wang K;Cui L;Li W;Zhao X;Liu F;Wu M;Deng G;Ding W;Jia H;Li Z
许多研究表明，microRNA-210(miR-210)在低氧状态下表达强烈上调，并在大多数类型的癌细胞中进行差异调控。然而，miR-210在儿童急性淋巴细胞白血病(ALL)中的临床意义及其对白血病细胞对化疗药物反应的影响尚不清楚。本研究采用实时荧光定量聚合酶链式反应检测114例初诊ALL患儿骨髓标本中miR-210的表达，探讨miR-210的预后意义，并探讨其与ALL常见临床特征和治疗结果的关系。我们进一步研究了它对REH和RS4；11细胞系对化疗药物反应的影响。结果显示，复发组和诱导失败组miR210的表达显著低于其他组(P<；0.001)。利用受试者工作特征曲线，选择3.8243作为我们测试队列中miR210表达的分界值(38例)。低表达组的治疗结果明显较差(P<；0.05)，并在验证队列中得到验证(76例，P<；0.05)。诱导结束时miR210低表达且微小残留病阳性的患者，其复发或诱导失败的发生率明显高于未诱导者(P=0.001)。增加或降低miR-210的表达可增强或降低Reh细胞和RS4-11细胞对柔红霉素/地塞米松/L-天冬酰胺酶和柔红霉素/地塞米松/长春新碱的反应。综上所述，miR-210可能是一个良好的预后因子和药物敏感性的有用预测因子，是儿童ALL潜在的治疗靶点。
Many studies have demonstrated that microRNA-210 (miR-210) expression is intensively upregulated in hypoxic states and differentially regulated in most types of cancer cells. However, the clinical significance of miR-210 and its effects on the response of leukemic cells to chemotherapeutic drugs in childhood acute lymphoblastic leukemia (ALL) remain unknown. In the current study, using real-time qRT-PCR to detect miR-210 expression in bone marrow samples from 114 children at initial diagnosis of ALL, we investigated the prognostic significance of miR-210 and determined its associations with common clinical characteristics and treatment outcome. We further examined its effect on the response to chemotherapeutic drugs in the Reh and RS4;11 cell lines. Results showed that miR-210 expression was significantly lower in patients suffering from relapse and induction failure than in other patients (P < 0.001). Using the receiver operating characteristic curve, 3.8243 was selected as the cut-off value of miR-210 expression in our test cohort (38 cases). A significantly poorer treatment outcome (P < 0.05) was found in the low-expression group and verified in the validation cohort (76 cases, P < 0.05). Patients with low expression of miR-210 and positive minimal residual disease at the end of induction had a much higher rate of relapse or induction failure (P = 0.001). Increasing/decreasing miR-210 expression using agomir/antagomir could enhance or reduce the response of Reh cells and RS4;11 cells to daunorubicin/dexamethasone/L-asparaginase and daunorubicin/dexamethasone/vincristine, respectively. In conclusion, miR-210 may be a good prognostic factor and a useful predictor of drug sensitivity, and is a potential therapeutic target for pediatric ALL.
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DOI：
10.4161/cc.9.6.11006
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Chan SY;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
37.8
作者：
Hu S;Huang M;Li Z;Jia F;Ghosh Z;Lijkwan MA;Fasanaro P;Sun N;Wang X;Martelli F;Robbins RC;Wu JC
通讯作者：
Wu JC
影响因子：
4.8
作者：
Kim, Ha Won;Haider, Husnain K.;Ashraf, Muhammad
通讯作者：
Ashraf, Muhammad
影响因子：
9.8
作者：
Cefalu, Angelo B.;Calvo, Pier L.;Averna, Maurizio R.
通讯作者：
Averna, Maurizio R.
影响因子：
12.4
作者：
Puissegur, M-P;Mazure, N. M.;Mari, B.
通讯作者：
Mari, B.