A semantics-oriented computational approach to investigate microRNA regulation on glucocorticoid resistance in pediatric acute lymphoblastic leukemia.
A semantics-oriented computational approach to investigate microRNA regulation on glucocorticoid resistance in pediatric acute lymphoblastic leukemia.
复制标题
一种以语义为导向的计算方法，用于研究小儿急性淋巴细胞白血病中糖皮质激素耐药性的microRNA调节。
DOI：
10.1186/s12911-018-0637-3
复制
发表时间：
2018-07-23
影响因子：
3.5
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Chen H;Zhang D;Zhang G;Li X;Liang Y;Kasukurthi MV;Li S;Borchert GM;Huang J
急性淋巴细胞白血病是儿童中最常见的肿瘤。尽管最先进的治疗策略取得了巨大成就，但耐药性仍然是导致儿童急性淋巴细胞白血病化疗失败并导致复发的主要原因。这种现象的内在机制尚不清楚，有待进一步探讨。先前的研究表明，microRNA可以作为许多耐药相关基因的转录后调节因子。然而，儿童急性淋巴细胞白血病中microRNA调控机制的细节远未完全了解。我们利用基于新兴生物医学和生物本体和语义技术的计算方法来研究microRNA：mRNA调控对儿童急性淋巴细胞白血病糖皮质激素耐药的重要作用。特别是，基于用户提供的MeSH术语设计了各种过滤机制，以有效的方式缩小最有希望的microRNA。在我们对背景文献的人工搜索中，我们发现了总共18种可能调节儿童急性淋巴细胞白血病糖皮质激素抵抗的候选microRNA。在使用更广泛的匹配选项进行第一轮过滤后，其中使用了用户提供的MeSH项及其直接父项，18种microRNA的靶标数量从232减少到74。在使用精确匹配选项的第二轮过滤期间，仅使用MeSH项本身，目标数量进一步减少到19个。最后，我们在OmniSearch软件工具中对五种可能的调节microRNA进行了语义搜索，并确定了两种最可能的microRNA。我们成功地鉴定了两种microRNA，hsa-miR-142- 3 p和hsa-miR-17- 5 p，它们被计算预测与糖皮质激素耐药密切相关，因此可能作为儿科急性淋巴细胞白血病的新生物标志物和治疗靶点。
Acute lymphoblastic leukemia is the most prevalent neoplasia among children. Despite the tremendous achievements of state-of-the-art treatment strategies, drug resistance is still a major cause of chemotherapy failure leading to relapse in pediatric acute lymphoblastic leukemia. The underlying mechanisms of such phenomenon are not yet clear and subject to further exploration. Prior research has shown that microRNAs can act as post-transcriptional regulators of many genes related to drug resistance. However, details of microRNA regulation mechanisms in pediatric acute lymphoblastic leukemia are far from completely understood. We utilized a computational approach based upon emerging biomedical and biological ontologies and semantic technologies to investigate the important roles of microRNA: mRNA regulation on glucocorticoid resistance in pediatric acute lymphoblastic leukemia. In particular, various filtering mechanisms were designed based on the user-provided MeSH term to narrow down the most promising microRNAs in an effective manner. During our manual search on background literature, we found a total of 18 candidate microRNAs that possibly regulate glucocorticoid resistance in pediatric acute lymphoblastic leukemia. After the first-round filtering using the Broader-Match option where both the user-provided MeSH term and its direct parent term were utilized, the number of targets for 18 microRNAs was reduced from 232 to 74. During the second-round filtering with the Exact-Match option where only the MeSH term itself was utilized, the number of targets was further reduced to 19. Finally, we conducted semantic searches in the OmniSearch software tool on the five likely regulating microRNAs and identified two most likely microRNAs. We successfully identified two microRNAs, hsa-miR-142-3p and hsa-miR-17-5p, which are computationally predicted to closely relate to glucocorticoid resistance, thus potentially serving as novel biomarkers and therapeutic targets in pediatric acute lymphoblastic leukemia.
登录
查看更多内容
一组参与耐药性和白血病干细胞分化途径的 miRNA 与儿童 ALL 的复发风险和糖皮质激素反应相关
影响因子：
3.5
作者：
Han BW;Feng DD;Li ZG;Luo XQ;Zhang H;Li XJ;Zhang XJ;Zheng LL;Zeng CW;Lin KY;Zhang P;Xu L;Chen YQ
通讯作者：
Chen YQ
影响因子：
2.6
作者：
Harada, Masako;Pokrovskaja-Tamm, Katja;Corcoran, Martin
通讯作者：
Corcoran, Martin
影响因子：
2.6
作者：
Yang, Apeng;Ma, Jiexian;Xie, Yanhui
通讯作者：
Xie, Yanhui
影响因子：
11.4
作者：
Rainer, J.;Ploner, C.;Kofler, R.
通讯作者：
Kofler, R.
影响因子：
20.3
作者：
Kotani, Ai;Ha, Daon;Lodish, Harvey F.
通讯作者：
Lodish, Harvey F.