Department of Cardiothoracic Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Yonsei Med J. 2020 Mar;61(3):210-217. doi: 10.3349/ymj.2020.61.3.210.
The goal of this study was to explore the effects of hsa-let-7g on cell proliferation and apoptosis, and elucidate its role in lung cancer development.
The expression levels of has-let-7g and HOXB1 in tissues and cells were measured by qRT-PCR. An inhibitor of hsa-let-7g or one targeting a control messenger RNA were transfected into A549 and H1944 lung cancer cells, and the effects of hsa-let-7g dysregulation on cell viability and apoptosis were analyzed using CCK-8 and apoptosis detection assays. HOXB1 was confirmed as the target gene of hsa-let-7g, based on luciferase reporter assay results. The relationship between hsa-let-7g and HOXB1 was confirmed by co-transfection of inhibitors of hsa-let-7g and HOXB1 followed by Western blot, CCK-8, and apoptosis detection assays.
We observed high expression of hsa-let-7g in lung cancer tissues compared to the corresponding normal tissues, and generally higher expression of hsa-let-7g in patients with advanced tumor classification. The results of CCK-8 and apoptosis detection experiments showed that the inhibition of hsa-let-7g significantly inhibited proliferation of A549 and H1944 cells, but also promoted apoptosis. HOXB1 is a specific target of hsa-let-7g, and downregulation of HOXB1 in lung cancer cells reversed the suppressive effects caused by knocking down hsa-let-7g.
These data collectively suggest that the expression of hsa-let-7g inhibits lung cancer cells apoptosis and promotes proliferation by down-regulating HOXB1. The results from this study demonstrate the potential of hsa-let-7g/HOXB1 axis as a therapeutic target for the treatment of lung cancer.
本研究旨在探讨 hsa-let-7g 对细胞增殖和凋亡的影响,并阐明其在肺癌发展中的作用。
通过 qRT-PCR 测量组织和细胞中 hsa-let-7g 和 HOXB1 的表达水平。将 hsa-let-7g 的抑制剂或针对对照信使 RNA 的抑制剂转染到 A549 和 H1944 肺癌细胞中,并用 CCK-8 和凋亡检测分析 hsa-let-7g 失调对细胞活力和凋亡的影响。根据荧光素酶报告基因检测结果,证实 HOXB1 是 hsa-let-7g 的靶基因。通过共转染 hsa-let-7g 和 HOXB1 的抑制剂,然后进行 Western blot、CCK-8 和凋亡检测分析,证实了 hsa-let-7g 和 HOXB1 之间的关系。
我们观察到肺癌组织中 hsa-let-7g 的表达高于相应的正常组织,并且在肿瘤分级较高的患者中 hsa-let-7g 的表达通常较高。CCK-8 和凋亡检测实验的结果表明,抑制 hsa-let-7g 显著抑制 A549 和 H1944 细胞的增殖,但也促进凋亡。HOXB1 是 hsa-let-7g 的特异性靶基因,下调肺癌细胞中的 HOXB1 逆转了敲低 hsa-let-7g 引起的抑制作用。
这些数据表明,hsa-let-7g 的表达通过下调 HOXB1 抑制肺癌细胞凋亡并促进增殖。本研究的结果表明,hsa-let-7g/HOXB1 轴作为治疗肺癌的潜在治疗靶点。