Dal Bo Michele, Bomben Riccardo, Hernández Luis, Gattei Valter
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano PN, Italy.
Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Oncotarget. 2015 Aug 14;6(23):19381-92. doi: 10.18632/oncotarget.4574.
MicroRNAs (miRNAs) represent a class of small non-coding single-stranded RNA molecules acting as master regulators of gene expression post transcriptionally by inhibiting the translation or inducing the degradation of target messenger RNAs (mRNAs). In particular, the miR-17-92 cluster is widely expressed in many different cell types and is essential for many developmental and pathogenic processes. As a strong oncogene, miR-17-92 can regulate multiple cellular processes that favor malignant transformation, promoting cell survival, rapid cell proliferation, and increased angiogenesis. The miR-17-92 cluster has been reported to be involved in hematopoietic malignancies including diffuse large B-cell lymphoma, mantle cell lymphoma, Burkitt's lymphoma, and chronic lymphocytic leukemia. Given the multiple and potent effects on cellular proliferation and apoptosis exerted by the miR-17-92 cluster, miRNAs belonging to the cluster surely represent attractive targets for cancer therapy also in the context of lymphoproliferative disorders. In the present review, we focus on the role of the miR-17-92 cluster in lymphoproliferative disorders, including diagnostic/prognostic implications, and on the potential applications of anti-miRNAs based therapies targeting miRNAs belonging to the cluster.
微小RNA(miRNA)是一类小的非编码单链RNA分子,通过抑制翻译或诱导靶信使RNA(mRNA)降解,在转录后作为基因表达的主要调节因子发挥作用。特别是,miR-17-92簇在许多不同细胞类型中广泛表达,对许多发育和致病过程至关重要。作为一种强大的癌基因,miR-17-92可以调节多个有利于恶性转化的细胞过程,促进细胞存活、快速细胞增殖和增加血管生成。据报道,miR-17-92簇参与了包括弥漫性大B细胞淋巴瘤、套细胞淋巴瘤、伯基特淋巴瘤和慢性淋巴细胞白血病在内的血液系统恶性肿瘤。鉴于miR-17-92簇对细胞增殖和凋亡具有多种强大作用,该簇中的miRNA无疑也是淋巴增殖性疾病背景下癌症治疗的有吸引力的靶点。在本综述中,我们重点关注miR-17-92簇在淋巴增殖性疾病中的作用,包括诊断/预后意义,以及基于抗miRNA疗法靶向该簇中miRNA的潜在应用。