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miRNAs 在慢性淋巴细胞白血病发病机制和治疗耐药中的基石作用——重点关注信号通路的相互作用。

miRNAs as cornerstones in chronic lymphocytic leukemia pathogenesis and therapeutic resistance- An emphasis on the interaction of signaling pathways.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, 11231, Cairo, Egypt.

Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, 11231, Cairo, Egypt; Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt.

出版信息

Pathol Res Pract. 2023 Mar;243:154363. doi: 10.1016/j.prp.2023.154363. Epub 2023 Feb 8.

Abstract

Chronic lymphocytic leukemia (CLL) accounts for the vast majority of cases of leukemia. Patients of advanced age are more likely to develop the condition, which has a highly varied clinical course. Consideration of illness features and preceding treatment sequence, as well as patient preferences and comorbidities, is necessary for selecting the appropriate treatment for the appropriate patient. Therefore, there is an urgent need for novel biomarkers with high sensitivity and specificity to detect CLL early, monitor CLL patients, select the treatment responders, and reduce ineffective treatment, unwanted side effects, and unnecessary expenses. In both homeostasis and illness, microRNAs (miRNAs/miRs) play a vital role as master regulators of gene expression and, by extension, protein expression. MiRNAs typically reduce the stability of mRNAs, including those encoding genes involved in tumorigenesis processes as cell cycle regulation, inflammation, stress response, angiogenesis, differentiation, apoptosis, and invasion. Due to their unique properties, miRNAs are rapidly being exploited as accurate biomarkers for illness detection, and medicines based on miRNA targets are finding widespread application in clinical practice. Accordingly, the current review serves as a quick primer on CLL and the biogenesis of miRNAs. In addition to providing a brief overview of the miRNAs whose function in the progression of CLL has been established by recent in vitro or in vivo research through articulating the influence of these miRNAs on a wide variety of cellular functions, including increased proliferative potential; support for angiogenesis; cell cycle aberration; evasion of apoptosis; promotion of metastasis; and reduced sensitivity to specific treatments.

摘要

慢性淋巴细胞白血病(CLL)占白血病病例的绝大多数。高龄患者更易患该病,其临床表现差异很大。在为患者选择合适的治疗方案时,必须考虑疾病特征和既往治疗顺序,以及患者的偏好和合并症。因此,迫切需要高灵敏度和特异性的新型生物标志物,以早期发现 CLL,监测 CLL 患者,选择治疗应答者,并减少无效治疗、不必要的副作用和费用。在生理和疾病状态下,微小 RNA(miRNA/miRs)作为基因表达的主要调控因子,发挥着至关重要的作用,进而影响蛋白质的表达。miRNA 通常会降低 mRNA 的稳定性,包括那些编码参与肿瘤发生过程的基因,如细胞周期调控、炎症、应激反应、血管生成、分化、凋亡和侵袭。由于其独特的性质,miRNA 正在迅速被用作疾病检测的准确生物标志物,基于 miRNA 靶点的药物也正在临床实践中得到广泛应用。因此,本综述简要介绍了 CLL 及 miRNA 生成。除了简要概述通过阐述这些 miRNA 对多种细胞功能的影响,确定了其在 CLL 进展中具有功能的 miRNA 之外,还包括增加增殖潜能;支持血管生成;细胞周期异常;逃避细胞凋亡;促进转移;以及降低对特定治疗的敏感性。

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