Wang Huimin, Gou Xuxu, Jiang Tang, Ouyang Juan
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, China.
Department of Laboratory Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road II, Guangzhou, 510080, Guangdong, China.
J Cancer Res Clin Oncol. 2017 Jun;143(6):1005-1011. doi: 10.1007/s00432-017-2388-4. Epub 2017 Mar 12.
Glucocorticoids (GCs) are of wide usage in the clinical treatment of lymphoblastic malignancies such as acute lymphoblastic leukemia. However, individually distinctive responsiveness to the GC therapy may attenuate their clinical efficacy, and more reliable predictor for GC resistance is still eagerly needed. Recent studies indicate that microRNAs (miRNAs), which demonstrate regulatory functions targeting mRNAs during the post-transcription, involved in the regulation of GCs sensitivity through several mechanisms, especially adjusting the magnitude of GC receptors (GRs), which mediates the cellular effects of GCs and plays a pivotal role in GCs sensitivity, inspiring that special miRNAs pattern could serve as the biomarkers to predict GC sensitivity and bring forth potential strategies for overcoming drug resistance. In this review, we discuss related miRNAs and their diverse effects exerted on multifaceted complexity of GCs responsiveness for further exploiting the molecular mechanism of GC resistance and future construction of the molecular diagnostic method and reverse GC resistance.
We have reviewed and searched for eligible literature relating to the effects of microRNAs on GC responsiveness from systematic PubMed searches.
GC response can be mediated by miRNAs through influence on GC signaling pathway, leading to diverse glucocorticoid responsiveness. Mutations in miRNA gene also influence GC response. As well, GCs regulate the function of several miRNAs, and suggesting a bidirectional influence among them.
It is possible and necessary that miRNAs serve as stable biomarkers and GC resistant patients would benefit from an effective and early screening test.
糖皮质激素(GCs)在急性淋巴细胞白血病等淋巴细胞恶性肿瘤的临床治疗中广泛应用。然而,个体对GC治疗的独特反应性可能会削弱其临床疗效,因此仍迫切需要更可靠的GC抵抗预测指标。最近的研究表明,微小RNA(miRNAs)在转录后对mRNA具有靶向调控功能,通过多种机制参与GCs敏感性的调节,尤其是调节GC受体(GRs)的水平,GRs介导GCs的细胞效应并在GCs敏感性中起关键作用,这提示特定的miRNAs模式可作为预测GCs敏感性的生物标志物,并为克服耐药性提供潜在策略。在本综述中,我们讨论相关的miRNAs及其对GCs反应多方面复杂性的不同影响,以进一步探索GC抵抗的分子机制,构建分子诊断方法及逆转GC抵抗。
我们通过系统检索PubMed,查阅并筛选了与微小RNA对GC反应影响相关的合格文献。
miRNAs可通过影响GC信号通路介导GC反应,导致不同的糖皮质激素反应性。miRNA基因的突变也会影响GC反应。此外,GCs调节多种miRNAs的功能,提示它们之间存在双向影响。
miRNAs作为稳定的生物标志物是可能且必要的,GC抵抗患者将受益于有效且早期的筛查检测。