Vaz Megan, Watson Katrina L, Moorehead Roger A
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Mol Carcinog. 2025 Aug;64(8):1392-1407. doi: 10.1002/mc.23937. Epub 2025 Jun 11.
Studies from our lab demonstrated that increasing miR-200 expression in human triple negative breast cancer (TNBC) reduced tumor growth and metastasis In Vivo. In this study, we found that overexpression of miR-200s in TNBC cells significantly reduced the expression of JAG1. When JAG1 was knocked out in MDA-MB-231 cells proliferation and invasion were significantly reduced In Vitro. Moreover, loss of JAG1 inhibited mammary tumor growth and metastasis In Vivo. RNA sequencing revealed that loss of JAG1 altered the expression of genes associated with the ECM, angiogenesis, and EMT. These results imply that miR-200s may mediate some of their antitumor actions through reducing JAG1 expression and suggest that agents targeting JAG1 should be further evaluated as a therapeutic strategy for TNBC.
我们实验室的研究表明，在人三阴性乳腺癌（TNBC）中增加miR-200的表达可在体内减少肿瘤生长和转移。在本研究中，我们发现TNBC细胞中miR-200s的过表达显著降低了JAG1的表达。当JAG1在MDA-MB-231细胞中被敲除时，体外增殖和侵袭显著降低。此外，JAG1的缺失在体内抑制了乳腺肿瘤的生长和转移。RNA测序显示，JAG1的缺失改变了与细胞外基质、血管生成和上皮-间质转化相关基因的表达。这些结果表明，miR-200s可能通过降低JAG1的表达来介导其一些抗肿瘤作用，并提示靶向JAG1的药物应作为TNBC的治疗策略进行进一步评估。
