DGCR8 promotes the metastasis in triple-negative breast cancer by epigenetically regulating TGF-β
DGCR8 promotes the metastasis in triple-negative breast cancer by epigenetically regulating TGF-β
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DOI：
10.26355/eurrev_202003_20523
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Ren, Z-X
中科院分区：
文献类型：
--
作者：
Cui, C-Y;Pan, Q-W;Ren, Z-X
目的：乳腺癌是最常见的致命性癌症之一。最近的研究已经确定了基因在三阴性乳腺癌(TNBC)的发生和发展中的重要作用。本研究以Dgcr8为研究对象，探讨其在肿瘤转移中的作用。患者和方法：采用实时定量聚合酶链式反应(qRT-PCR)检测50例TNBC患者组织中Dgcr8的表达。采用创伤愈合实验和Transwell实验观察下调或过表达Dgcr8对TNBC细胞生物学行为的影响。此外，通过qRT-PCR和Western印迹分析，发现了Dgcr8在TNBC中的潜在靶蛋白。结果：Dgcr8在TNBC组织中的表达水平高于癌旁组织。此外，沉默Dgcr8后，TNBC细胞的迁移能力和侵袭能力受到抑制，而过表达Dgcr8后，其侵袭能力和迁移能力增强。此外，在TNBC细胞中，Dgcr8沉默后，转化生长因子-β表达下调，而在TNBC细胞中过表达转化生长因子-β。此外，转化生长因子-β在TNBC组织中表达上调，与Dgcr8呈正相关。结论：本研究在TNBC中发现了一个新的癌基因，提示Dgcr8可通过靶向转化生长因子-β促进TNBC细胞的迁移和侵袭，为TNBC患者提供了一个新的治疗靶点。
OBJECTIVE: Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of genes in the development and progression of Tri-negative breast cancer (TNBC). In this research, DGCR8 was studied to identify how it functioned in the metastasis of TNBC. PATIENTS AND METHODS: DGCR8 expression of tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRTPCR) in 50 TNBC patients. Wound healing assay and transwell assay were used to observe the changes in the biological behaviors of TNBC cells through knockdown or overexpression of DGCR8. In addition, qRT-PCR and Western blot assay were performed to discover the potential target protein of DGCR8 in TNBC. RESULTS: DGCR8 expression level in TNBC samples was higher than that of adjacent ones. Besides, the migration ability and invasion ability of TNBC cells were inhibited after DGCR8 was silenced, while they were promoted after DGCR8 was overexpressed. In addition, TGF-beta was downregulated after silencing of DGCR8 in TNBC cells, while TGF-beta was upregulated after overexpression of DGCR8 in TNBC cells. Furthermore, TGF-beta was upregulated in TNBC tissues, which was positively associated with DGCR8. CONCLUSIONS: Our study uncovers a new oncogene in TNBC and suggests that DGCR8 can enhance TNBC cell migration and invasion via targeting TGF-beta, which provides a novel therapeutic target for TNBC patients.