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miR-34b-3p 通过靶向 CDK4 抑制非小细胞肺癌(NSCLC)中的细胞增殖、细胞周期进程和细胞凋亡。

MiR-34b-3p represses cell proliferation, cell cycle progression and cell apoptosis in non-small-cell lung cancer (NSCLC) by targeting CDK4.

机构信息

Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China.

Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, China.

出版信息

J Cell Mol Med. 2019 Aug;23(8):5282-5291. doi: 10.1111/jcmm.14404. Epub 2019 Jun 14.

Abstract

Lung cancer is the most common incident cancer, with a high mortality worldwide, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of cases. Numerous studies have shown that the aberrant expression of microRNAs (miRNAs) is associated with the development and progression of cancers. However, the clinical significance and biological roles of most miRNAs in NSCLC remain elusive. In this study, we identified a novel miRNA, miR-34b-3p, that suppressed NSCLC cell growth and investigated the underlying mechanism. miR-34b-3p was down-regulated in both NSCLC tumour tissues and lung cancer cell lines (H1299 and A549). The overexpression of miR-34b-3p suppressed lung cancer cell (H1299 and A549) growth, including proliferation inhibition, cell cycle arrest and increased apoptosis. Furthermore, luciferase reporter assays confirmed that miR-34b-3p could bind to the cyclin-dependent kinase 4 (CDK4) mRNA 3'-untranslated region (3'-UTR) to suppress the expression of CDK4 in NSCLC cells. H1299 and A549 cell proliferation inhibition is mediated by cell cycle arrest and apoptosis with CDK4 interference. Moreover, CDK4 overexpression effectively reversed miR-34-3p-repressed NSCLC cell growth. In conclusion, our findings reveal that miR-34b-3p might function as a tumour suppressor in NSCLC by targeting CDK4 and that miR-34b-3p may, therefore, serve as a biomarker for the diagnosis and treatment of NSCLC.

摘要

肺癌是最常见的癌症,全球死亡率很高,非小细胞肺癌(NSCLC)约占病例的 85%。许多研究表明,microRNAs(miRNAs)的异常表达与癌症的发生和发展有关。然而,大多数 miRNA 在 NSCLC 中的临床意义和生物学作用仍不清楚。在这项研究中,我们鉴定了一种新型 miRNA,miR-34b-3p,它抑制 NSCLC 细胞生长,并研究了其潜在机制。miR-34b-3p 在 NSCLC 肿瘤组织和肺癌细胞系(H1299 和 A549)中均下调。miR-34b-3p 的过表达抑制肺癌细胞(H1299 和 A549)生长,包括增殖抑制、细胞周期停滞和凋亡增加。此外,荧光素酶报告基因实验证实,miR-34b-3p 可以与细胞周期蛋白依赖性激酶 4(CDK4)mRNA 3'-非翻译区(3'-UTR)结合,从而抑制 NSCLC 细胞中 CDK4 的表达。H1299 和 A549 细胞增殖抑制是通过细胞周期停滞和凋亡介导的,CDK4 干扰。此外,CDK4 的过表达有效地逆转了 miR-34-3p 抑制 NSCLC 细胞生长。总之,我们的研究结果表明,miR-34b-3p 可能通过靶向 CDK4 发挥 NSCLC 肿瘤抑制作用,因此,miR-34b-3p 可能作为 NSCLC 诊断和治疗的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69a9/6652730/a337041cdfcc/JCMM-23-5282-g001.jpg

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