LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa-mir-22-3p
LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa-mir-22-3p
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DOI：
10.1002/jcp.26215
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发表时间：
2018-05-01
影响因子：
5.6
通讯作者：
Pan, Jing
中科院分区：
文献类型：
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作者：
Dong, Hui-Xing;Wang, Ren;Pan, Jing
长链非编码rna （lncRNAs）在包括肺腺癌（LUAD）在内的多种癌症的发病机制中发挥着关键作用。因此，在本研究中，我们旨在探讨lncRNA diggeorge综合征关键区基因5 （DGCR5）在LUAD中的生物学和临床意义。我们观察到DGCR5在LUAD组织和LUAD细胞系中表达上调。抑制DGCR5可通过抗凋亡作用阻止LUAD的进展。下调DGCR5可使BCL-2 mRNA表达量和蛋白水平升高，BAX则相反。此外，通过生物信息学搜索发现了DGCR5的一个新的microRNA靶点hsa-mir-22-3p，并通过双荧光素酶报告系统进行了确认。为了验证DGCR5是否通过体外调节hsa-mir-22-3p发挥其生物学功能，我们进行了功能增益和功能丧失研究。DGCR5的过表达能够逆转hsa-mir-22-3p模拟物的肿瘤抑制作用。此外，建立了肿瘤异种移植物体内实验，以检测DGCR5在LUAD肿瘤发生中的功能。DGCR5表达下调与较小的肿瘤大小密切相关，提示LUAD患者预后良好。综上所述，DGCR5可作为LUAD诊断和治疗的预后生物标志物和治疗靶点。
Long non-coding RNAs (lncRNAs) serve critical roles in the pathogenesis of various cancers, including lung adenocarcinoma (LUAD). Herein, in this study, we aimed to investigate the biological and clinical significance of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in LUAD. It was observed that DGCR5 was upregulated in LUAD tissues and LUAD cell lines. Inhibition of DGCR5 can prevent LUAD progression via playing anti-apoptosis roles. Both mRNA expression and protein levels of BCL-2 were increased by DGCR5 downregulation while reversely BAX was increased. Additionally, a novel microRNA target of DGCR5, hsa-mir-22-3p was identified through bioinformatics search and confirmed by dual-luciferase reporter system. Gain and loss-of-function studies were performed to verify whether DGCR5 exerts its biological functions through regulating hsa-mir-22-3p in vitro. Overexpression of DGCR5 was able to reverse the tumor inhibitory effect of hsa-mir-22-3p mimics. Furthermore, in vivo tests tumor xenografts were established to detect the function of DGCR5 in LUAD tumorigenesis. Downregulated DGCR5 expression was greatly associated with smaller tumor size, implying a favorable prognosis of LUAD patients. Taken these together, DGCR5 could be considered as a prognostic biomarker and therapeutic target in LUAD diagnosis and treatment.