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miRNA-100 通过靶向 HOXA1 调控上皮-间充质转化和 Wnt/β-catenin 通路发挥抑癌作用在非小细胞肺癌中

microRNA-100 functions as a tumor suppressor in non-small cell lung cancer via regulating epithelial-mesenchymal transition and Wnt/β-catenin by targeting HOXA1.

机构信息

Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Cardiothoracic Surgey, Yantaishan Hospital, Yantai, China.

出版信息

Thorac Cancer. 2020 Jun;11(6):1679-1688. doi: 10.1111/1759-7714.13459. Epub 2020 May 4.

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is a leading subtype in lung cancer, with high morbidities and mortalities worldwide. microRNA (miRNA) has appeared to play indispensable roles in a variety of solid carcinomas. The current study focused on the functions of miR-100 in NSCLC.

METHODS

qRT-PCR was performed to detect miR-100 and HOXA1 expressions in NSCLC tissues and cells. MTT and transwell assays were used to determine the functions of miR-100 in NSCLC cell proliferation, invasion and migration abilities. Western blot was used to measure related protein expressions.

RESULTS

qRT-PCR results showed that miR-100 expressions were dramatically decreased in NSCLC tissues. MTT assays indicated that miR-100 restoration inhibited NSCLC cell proliferation. Furthermore, transwell assay was performed to determine the impacts of miR-100 on NSCLC invasion and migration abilities. As expected, the invasion and migration capacities were significantly repressed. Direct interactions between HOXA1 and miR-100 were also verified via dual-luciferase reporter assays. Western blot analysis demonstrated that miR-100 exerted suppressive functions via regulating EMT and Wnt/β-catenin in NSCLC cells.

CONCLUSIONS

Our results showed that miR-100 served antitumor roles in NSCLC, providing new evidence of miR-100 as a promising therapeutic biomarker in NSCLC.

摘要

背景

非小细胞肺癌(NSCLC)是肺癌的主要亚型,在全球范围内发病率和死亡率都很高。microRNA(miRNA)在各种实体癌中似乎发挥着不可或缺的作用。本研究重点研究了 miR-100 在 NSCLC 中的功能。

方法

采用 qRT-PCR 检测 NSCLC 组织和细胞中 miR-100 和 HOXA1 的表达。MTT 和 Transwell 实验用于检测 miR-100 对 NSCLC 细胞增殖、侵袭和迁移能力的影响。Western blot 用于检测相关蛋白的表达。

结果

qRT-PCR 结果表明,miR-100 在 NSCLC 组织中的表达明显降低。MTT 实验表明 miR-100 恢复抑制 NSCLC 细胞增殖。此外,Transwell 实验用于确定 miR-100 对 NSCLC 侵袭和迁移能力的影响。正如预期的那样,侵袭和迁移能力显著受到抑制。双荧光素酶报告实验验证了 HOXA1 和 miR-100 之间的直接相互作用。Western blot 分析表明,miR-100 通过调节 EMT 和 Wnt/β-catenin 在 NSCLC 细胞中发挥抑制作用。

结论

我们的结果表明,miR-100 在 NSCLC 中发挥抗肿瘤作用,为 miR-100 作为 NSCLC 有前途的治疗生物标志物提供了新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f41a/7262897/c17f706f96d5/TCA-11-1679-g001.jpg

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