《生命科学》 2024, 36(4): 561-570
LncRNA在慢性粒细胞白血病中的研究进展
摘 要:
慢性粒细胞白血病(chronic myeloid leukemia, CML) 是一种由BCR-ABL 融合基因驱动的骨髓恶性肿瘤。虽然酪氨酸激酶抑制剂(TKI) 可有效抑制BCR-ABL 活性,但耐药性仍然是治疗中的主要问题。长链非编码RNA (long non-coding RNA, lncRNA) 为长度大于200 个核苷酸的ncRNA,在肿瘤的发生、发展和耐药中扮演着重要角色。研究发现,lncRNA 通过与miRNA 互作调控下游信号通路,或影响表观遗传修饰等多种机制影响CML 细胞的增殖、凋亡和药物敏感性,是CML 的潜在药物靶点。同时,多项研究证明lncRNA 是CML 有效的诊断、预后生物标志物,如HOX 转录反义RNA (HOX transcript antisense RNA, HOTAIR) 可应用于CML 早期诊断、前列腺癌抗原3 (prostate cancer antigen 3, PCA3) 表达水平的改变可作为CML 的预后指标。现对CML 相关lncRNA 的作用机制、与CML 临床分期、耐药产生和预后的关系,以及作为诊断、预后生物标志物和药物靶点的研究进展作一综述。
通讯作者:张俊芳 , Email:jfzhang@shou.edu.cn
Abstract:
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by BCR-ABL fusion. Although tyrosine kinase inhibitors can effectively inhibit BCR-ABL activity, drug resistance is still a major problem in treatment. Long non-coding RNA (lncRNA) is a kind of ncRNA with a length of more than 200 nucleotides, lncRNAs play important roles in the initiation, development, and drug resistance of CML. In recent years, studies have found that lncRNAs affect the proliferation, apoptosis and drug sensitivity of CML cells by various mechanisms such as interacting with miRNA to regulate downstream signaling pathways, or affecting epigenetic modification, so lncRNAs are potential drug targets of CML. Meanwhile accumulating studies have proved that lncRNA is an effective diagnostic and prognostic biomarker of CML. For instance, HOX transcript antisense RNA (HOTAIR) can be applied to the early diagnosis of CML, and the change of prostate cancer antigen 3 (PCA3) expression level can be used as a prognostic indicator of CML. In this review, the mechanism of CMLrelated lncRNA, its relationship with CML clinical stage, drug resistance and prognosis, as well as its research progress as diagnostic and prognostic biomarkers and drug targets were summarized.
Communication Author:ZHANG Jun-Fang , Email:jfzhang@shou.edu.cn