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miR-138 的上调通过调节 EZH2 增加肝癌对顺铂的敏感性。

Upregulation of miR-138 Increases Sensitivity to Cisplatin in Hepatocellular Carcinoma by Regulating EZH2.

机构信息

Department of Pharmacy, First Affiliated Hospital, Gannan Medical College, Ganzhou, Jiangxi, China.

Department of Pharmacy, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.

出版信息

Biomed Res Int. 2021 Mar 6;2021:6665918. doi: 10.1155/2021/6665918. eCollection 2021.

DOI:10.1155/2021/6665918
PMID:33748276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7960019/
Abstract

Chemotherapeutic insensitivity is a major obstacle for effective treatment of hepatocellular carcinoma (HCC). Recently, new evidence showed that microRNAs (miRNAs) are closely related to drug sensitivity. This study aimed to investigate the relationship between miR-138 expression and cisplatin sensitivity of HCC cells by regulation of EZH2. CCK-8, EdU, and western blotting are determining the cell viability, proliferation, EZH2, and EMT-related protein expression. It was found that compared with normal samples, miR-138 expression was lower in cancer tissue; it was also downregulated in HCC cells. Transfected with miR-138 mimic increased sensitivity of HCC cells to cisplatin. Mechanistically, Luciferase Reporter analysis verified the interaction between miR-138 and target gene EZH2. Inhibition of EZH2 enhanced cisplatin sensitivity and transfection with EZH2 mimic mirrored the function of miR-138 in cisplatin sensitivity. Furthermore, the role of miR-138 on reversed cisplatin-induced epithelial-mesenchymal transition (EMT) was attenuated when combined with EZH2 plasmid. In conclusion, all data from this study illustrate that miR-138 may as a tumor suppressor provides a potential treatment method to treating HCC.

摘要

化疗不敏感是有效治疗肝细胞癌 (HCC) 的主要障碍。最近，新的证据表明 microRNAs (miRNAs) 与药物敏感性密切相关。本研究旨在通过调节 EZH2 来研究 miR-138 表达与 HCC 细胞顺铂敏感性之间的关系。CCK-8、EdU 和 Western blot 用于确定细胞活力、增殖、EZH2 和 EMT 相关蛋白表达。结果发现，与正常组织相比，miR-138 在癌组织中的表达较低；在 HCC 细胞中也下调。转染 miR-138 模拟物增加了 HCC 细胞对顺铂的敏感性。机制上，荧光素酶报告分析验证了 miR-138 与靶基因 EZH2 之间的相互作用。抑制 EZH2 增强了顺铂敏感性，转染 EZH2 模拟物模拟了 miR-138 对顺铂敏感性的作用。此外，当与 EZH2 质粒结合时，miR-138 对逆转顺铂诱导的上皮-间充质转化 (EMT) 的作用减弱。总之，本研究的所有数据表明，miR-138 可能作为一种肿瘤抑制因子为治疗 HCC 提供了一种潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/15ccf28bcf03/BMRI2021-6665918.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/5822c0c4a1c8/BMRI2021-6665918.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/7a476f785687/BMRI2021-6665918.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/d076ccc149d0/BMRI2021-6665918.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/394390097615/BMRI2021-6665918.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/c56afc49f25e/BMRI2021-6665918.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/15ccf28bcf03/BMRI2021-6665918.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/5822c0c4a1c8/BMRI2021-6665918.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/7a476f785687/BMRI2021-6665918.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/d076ccc149d0/BMRI2021-6665918.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/394390097615/BMRI2021-6665918.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/c56afc49f25e/BMRI2021-6665918.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4eb/7960019/15ccf28bcf03/BMRI2021-6665918.006.jpg

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