The RNA Binding Protein RBMS3 Inhibits the Metastasis of Breast Cancer by Regulating Twist1 Expression
The RNA Binding Protein RBMS3 Inhibits the Metastasis of Breast Cancer by Regulating Twist1 Expression
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RNA结合蛋白RBMS3通过调节Twist1表达抑制乳腺癌转移
DOI：
10.1186/s13046-019-1111-5
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
魏继福
中科院分区：
文献类型：
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作者：
朱磊;奚佩雯;李小霞;孙茜;周文斌;夏添松;石靓;胡玥;丁强;魏继福
背景转移仍然是乳腺癌治疗的最大障碍。因此，鉴定转移的特异性生物标志物是非常有必要的。 RNA 结合蛋白 3 (RBMS3) 在多种癌症中充当肿瘤抑制因子。然而，其在乳腺癌中的作用和分子机制尚不清楚。方法采用实时荧光定量PCR和蛋白质印迹法测定乳腺癌细胞和组织中RBMS3的表达。通过Transwell和体内转移实验研究RBMS3对乳腺癌细胞迁移、侵袭和转移的影响。应用转录组测序筛选受RBMS3影响的差异基因表达。采用RNA免疫沉淀法结合荧光素酶报告基因检测来探讨RBMS3与Twist1 mRNA之间的直接相关性。结果RBMS3在乳腺癌中表达下调，RBMS3的异位表达有助于抑制细胞体外迁移、侵袭和体内肺转移。此外，RBMS3 通过直接结合 Twist1 mRNA 的 3'-UTR 负向调节 Twsit1 表达，从而降低 Twist1 诱导的基质金属蛋白酶 2 (MMP2) 表达。此外，Twist1诱导的细胞迁移、侵袭和肺转移可以通过RBMS3的上调来逆转。结论总而言之，我们的研究揭示了RBMS3/Twsit1/MMP2轴在调节乳腺癌侵袭和转移中的新机制，这可能成为乳腺癌治疗的潜在分子标志物。
BackgroundMetastasis remains the biggest obstacle for breast cancer treatment. Therefore, identification of specific biomarker of metastasis is very necessary. The RNA binding protein 3 (RBMS3) acts as a tumor suppressor in various cancers. Whereas, its role and underlying molecular mechanism in breast cancer is far from elucidated.MethodsQuantitative real-time PCR and western blots were carried out to determine the expression of RBMS3 in breast cancer cells and tissues. Transwell and in vivo metastasis assay were conducted to investigate the effects of RBMS3 on migration, invasion and metastasis of breast cancer cells. Transcriptome sequencing was applied to screen out the differential gene expression affected by RBMS3. RNA immunoprecipitation assay combined with luciferase reporter assay were performed to explore the direct correlation between RBMS3 and Twist1 mRNA.ResultsRBMS3 was downregulated in breast cancer and ectopic expression of RBMS3 contributed to inhibition of cell migration, invasion in vitro and lung metastasis in vivo. Furthermore, RBMS3 negatively regulated Twsit1 expression via directly binding to 3′-UTR of Twist1 mRNA, and thereby decreased Twist1-induced expression of matrix metalloproteinase 2 (MMP2). Additionally, Twist1-induced cell migration, invasion and lung metastasis could be reversed by the upregulation of RBMS3.ConclusionsIn summary, our study revealed a novel mechanism of the RBMS3/Twsit1/MMP2 axis in the regulation of invasion and metastasis of breast cancer, which may become a potential molecular marker for breast cancer treatment.