The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1
The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1
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DOI：
10.3349/ymj.2020.61.3.210
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发表时间：
2020-03-01
影响因子：
2.4
通讯作者：
Ma, Shengwei
中科院分区：
文献类型：
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作者：
Cui, Fenghe;Zhou, Qian;Ma, Shengwei
目的：探讨hsA-let-7g对细胞增殖和凋亡的影响，探讨其在肺癌发生发展中的作用。材料与方法：采用定量RT-PCR方法检测hSA-let-7g和HOXB1在肺癌组织和细胞中的表达水平。将hSA-let-7g的抑制剂或靶向控制信使RNA的抑制剂分别导入A549和H1944肺癌细胞，用CCK-8和细胞凋亡检测分析hSA-let-7g调控失调对细胞活力和细胞凋亡的影响。根据荧光素酶报告基因检测结果，确定HOXB1为hsa-let-7g的目的基因。结果：肺癌组织中hSA-let-7g的表达明显高于相应的正常组织，晚期肺癌组织中hSA-let-7g的表达普遍高于正常组织。CCK-8和细胞凋亡检测实验结果表明，抑制hsa-let-7g明显抑制A549和H1944细胞的增殖，但也促进细胞凋亡。HOXB1是hsa-let-7g的特异性靶点，下调HOXB1可逆转hsa-let-7g的抑制作用。结论：hsa-let-7g通过下调HOXB1的表达抑制肺癌细胞的凋亡，促进肺癌细胞的增殖。本研究结果表明hSA-let-7G/HOXB1轴有可能成为肺癌治疗的靶点。
Purpose: 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.Materials and Methods: 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.Results: 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.Conclusion: 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.