摘要
miRNA-181是一个进化中极其保守的明星分子。在人类基因组中,miR-181家族成员包括miR-181a-1、miR-181a-2、miR-181b-2、miR-181b-2、miR-181c和miR-181d。miR-181最早是在小鼠B淋巴细胞中发现其特异高表达,且能调控早期造血系统的形成,从而引起了人们的关注。miR-181在小鼠胸腺、脑、肺等器官中高表达,骨髓和脾脏中也可检测到它的存在,而在造血前体细胞中低表达。其中,miR-181a被认为参与B细胞的分化成熟过程。其后,大量研究证实miR-181是一个重要的基因表达调控因子,功能涉及生物体免疫、炎症,细胞周期调控、细胞凋亡及分化等病理生理过程。另一方面miR-181在多种肿瘤中表达异常,包括白血病、神经母细胞瘤、神经胶质瘤等,但其功能及调控机制不太清楚。本文就miR-181分子的基因结构、基因表达与调控、生物学功能以及与疾病发生的相关性作一综述。
miR-181 is a highly conserved microRNA throughout many different species. In humans, there are six homologs (hsa-miR- 181 a- 1, hsa-miR- 181 a-2, hsa-miR- 181b- 1, hsa-miR- 181 b-2, hsa-miR- 181 c and hsa-miR- 181 d). It was preferentially expressed in the B-lymphoid cells of mouse bone marrow, and its ectopic expression in hematopoietic stem/progenitor cells led to an increased fraction of B-lineage cells in both tissue-culture differentiation assays and adult mice. miR-181 is highly expressed in the mouse thymus, brain, lungs, and its expression can also be detected in the bone marrow and spleen, while low expression is found in hematopoietic precursor cells, miR-181 a is involved in B cell differentiation and maturation process in this research. On one hand, targets of miR-181 include key proteins regulating innate immunity, inflammation,cell cycle, apoptosis and differentiation. On the other hand, miR-181 expression is abnormal in a variety of tumors, including leukemia, neuroblastoma, glioma and other tumors, but its function and regulation mechanism is not yet clear. Here we discuss the recent findings of miR-181 regarding gene structure, gene expression and regulation, biological function, and correlation with pathogenesis and progression of human disease.
出处
《现代生物医学进展》
CAS
2013年第9期1797-1800,1738,共5页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(81272310)
广东省自然科学基金(S2012020011020)