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MMSET的下调通过抑制Wnt/β-连环蛋白信号通路来损害乳腺癌的增殖和转移。

Downregulation of MMSET impairs breast cancer proliferation and metastasis through inhibiting Wnt/β-catenin signaling.

作者信息

Zhao Xiaohui, Xie Tian, Zhao Wenhui, Cai Wanhua, Su Xiaobo

机构信息

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China,

State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Cancer Center, Guangzhou 510060, China.

出版信息

Onco Targets Ther. 2019 Mar 14;12:1965-1977. doi: 10.2147/OTT.S196430. eCollection 2019.

DOI:10.2147/OTT.S196430
PMID:30936716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6421877/
Abstract

BACKGROUND

Recently, the biggest challenge in the treatment of breast cancer is the metastasis of breast cancer cells. Multiple myeloma SET protein (MMSET), a histone lysine methyltransferase, overexpressed in various human cancers, was reported to be associated with carcinogenesis of human cancers.

METHODS

Expression of MMSET in breast cancer cell lines and tissues was quantified by real-time PCR and Western blotting. Immunohistochemistry was employed to analyze MMSET expression in 163 clinicopathologically characterized breast cancer cases. Cell functional assays such as MTT assay, colony formation, BrdU assay, flow cytometry, wound healing, Transwell assay, and 3D culture were used to investigate the effect of MMSET in the development and metastasis of human breast cancer. Effects of MMSET on Wnt/β-catenin signaling pathway were further studied by using Western blotting analysis.

RESULTS

Our results showed that MMSET expression was markedly overexpressed in breast cancer cells and clinical specimens and was significantly correlated with patients' clinicopatho-logic characteristics and prognosis. Moreover, silencing endogenous MMSET significantly inhibited the proliferation, migration, and metastasis of breast cancer cells through inhibiting the Wnt/β-catenin pathway.

CONCLUSION

This study found that the downregulated expression of MMSET impaired proliferation and metastasis of human breast cancer through inhibiting Wnt/β-catenin signaling pathway. Notably, our results indicated that MMSET could be a useful biomarker for the prognosis of breast cancer.

摘要

背景

近年来，乳腺癌治疗中的最大挑战是乳腺癌细胞的转移。多发性骨髓瘤SET蛋白（MMSET）是一种组蛋白赖氨酸甲基转移酶，在多种人类癌症中过表达，据报道与人类癌症的发生有关。

方法

通过实时PCR和蛋白质免疫印迹法对MMSET在乳腺癌细胞系和组织中的表达进行定量。采用免疫组织化学方法分析163例具有临床病理特征的乳腺癌病例中MMSET的表达情况。运用MTT法、集落形成实验、BrdU实验、流式细胞术、伤口愈合实验、Transwell实验和三维培养等细胞功能实验，研究MMSET在人类乳腺癌发生和转移中的作用。通过蛋白质免疫印迹分析进一步研究MMSET对Wnt/β-连环蛋白信号通路的影响。

结果

我们的结果显示，MMSET在乳腺癌细胞和临床标本中明显过表达，且与患者的临床病理特征及预后显著相关。此外，沉默内源性MMSET可通过抑制Wnt/β-连环蛋白通路显著抑制乳腺癌细胞的增殖、迁移和转移。

结论

本研究发现，MMSET表达下调通过抑制Wnt/β-连环蛋白信号通路损害人类乳腺癌的增殖和转移。值得注意的是，我们的结果表明MMSET可能是乳腺癌预后的一个有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/430f257f0238/ott-12-1965Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/4102be07629c/ott-12-1965Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/e74f245af18e/ott-12-1965Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/23d820d20edb/ott-12-1965Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/edad40b9eea9/ott-12-1965Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/430f257f0238/ott-12-1965Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/4102be07629c/ott-12-1965Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/e74f245af18e/ott-12-1965Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/23d820d20edb/ott-12-1965Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/edad40b9eea9/ott-12-1965Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3de/6421877/430f257f0238/ott-12-1965Fig5.jpg

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