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miRNA hsa-let-7g 通过靶向 HOXB1 促进肺癌增殖并抑制细胞凋亡。

The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1.

机构信息

Department of Cardiothoracic Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, China.

出版信息

Yonsei Med J. 2020 Mar;61(3):210-217. doi: 10.3349/ymj.2020.61.3.210.

DOI:10.3349/ymj.2020.61.3.210
PMID:32102121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7044691/
Abstract

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.

摘要

目的

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。

材料和方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/5e36583c1311/ymj-61-210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/072c1a8f30ee/ymj-61-210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/b06fc65364ad/ymj-61-210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/fd94380a3a6b/ymj-61-210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/1d3c063162d1/ymj-61-210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/5e36583c1311/ymj-61-210-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/072c1a8f30ee/ymj-61-210-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/b06fc65364ad/ymj-61-210-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/fd94380a3a6b/ymj-61-210-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/1d3c063162d1/ymj-61-210-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62cd/7044691/5e36583c1311/ymj-61-210-g005.jpg

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