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miRNA-21 的过表达通过抑制 SMAD7 促进肝癌细胞的增殖和侵袭。

Overexpression of miRNA-21 Promotes the Proliferation and Invasion in Hepatocellular Carcinoma Cells via Suppressing SMAD7.

机构信息

Chronic Disease Management Center, Qingdao Sixth People's Hospital, Qingdao City, Shandong Province, China.

Department of Clinical Lab, Qingdao Sixth People's Hospital, Qingdao City, Shandong Province, China.

出版信息

Technol Cancer Res Treat. 2019 Jan 1;18:1533033819878686. doi: 10.1177/1533033819878686.

DOI:10.1177/1533033819878686
PMID:31554487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6763940/
Abstract

PURPOSE

This study aimed to explore the molecular mechanism of microRNA-21 and smad family member 7 in hepatocellular carcinoma.

METHOD

A total of 57 participants were divided into control group (healthy participants, n = 10) and hepatocellular carcinoma group (hepatocellular carcinoma patients, n = 37). The expression of microRNA-21 levels were first detected in these two groups. Cell transfection was performed on hepatoma cell lines, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay to reveal proliferation and invasion ability. Furthermore, the relation between microRNA-21 and smad family member 7 was revealed by luciferase reporter gene and RNA immunoprecipitation assay. Finally, a transplantation tumor model of breast cancer in mice was constructed.

RESULTS

The serum indicators including α-alanine aminotransferase, aspartate aminotransferase, and albumin were differentially expressed between hepatocellular carcinoma group and control group. Compared to the control group, there was a high expression of microRNA-21 in hepatocellular carcinoma group. Low expression of microRNA-21 inhibited the proliferation and invasion of HepG2.2.15 and Huh7-1.3 cells. Luciferase reporter gene and RNA innumoprecipitation assay showed that smad family member 7 was the target gene of microRNA-21. Moreover, mice model analysis showed that microRNA-21 might regulate the growth of the transplanted tumors in mice by targeting smad family member 7.

CONCLUSION

The upregulated microRNA-21 might participate in the proliferation and migration in cells of hepatocellular carcinoma via suppression of smad family member 7. Furthermore, serum indicators such as alanine aminotransferase, aspartate aminotransferase, and albumin might be used as serum diagnostic markers for hepatocellular carcinoma.

摘要

目的

本研究旨在探讨 microRNA-21 和 SMAD 家族成员 7 在肝癌中的分子机制。

方法

共纳入 57 名参与者,分为对照组(健康参与者,n=10)和肝癌组(肝癌患者,n=37)。首先检测两组 microRNA-21 水平的表达。对肝癌细胞系进行细胞转染,然后进行 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和 Transwell 检测,以揭示增殖和侵袭能力。进一步通过荧光素酶报告基因和 RNA 免疫沉淀检测揭示 microRNA-21 与 SMAD 家族成员 7 的关系。最后构建小鼠乳腺癌移植瘤模型。

结果

肝癌组和对照组的血清指标,包括丙氨酸氨基转移酶、天冬氨酸氨基转移酶和白蛋白,存在差异。与对照组相比,肝癌组 microRNA-21 表达较高。microRNA-21 低表达抑制 HepG2.2.15 和 Huh7-1.3 细胞的增殖和侵袭。荧光素酶报告基因和 RNA 免疫沉淀检测显示,SMAD 家族成员 7 是 microRNA-21 的靶基因。此外,小鼠模型分析表明,microRNA-21 可能通过靶向 SMAD 家族成员 7 调节小鼠移植瘤的生长。

结论

上调的 microRNA-21 可能通过抑制 SMAD 家族成员 7 参与肝癌细胞的增殖和迁移。此外,丙氨酸氨基转移酶、天冬氨酸氨基转移酶和白蛋白等血清指标可能作为肝癌的血清诊断标志物。

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