癌变
癌症研究
小RNA
基因敲除
E2F1
微泡
生物
外体
乳腺癌
下调和上调
三苯氧胺
基因沉默
癌症
细胞凋亡
细胞周期
基因
生物化学
遗传学
作者
Yan Zhao,Lijun Jin,Xiaoyu Zhang
出处
期刊:Aging
[Impact Journals, LLC]
日期:2021-07-22
卷期号:13 (14): 18498-18514
被引量:14
标识
DOI:10.18632/aging.203298
摘要
Breast cancer (BC) is a common malignant tumor in females. The challenge in treating BC is overcoming chemoresistance. Exosome-mediated transfer of miRNAs is a molecule-shuttle in intercellular communication. Thus, we aimed to investigate whether exosomal miRNA-205 could affect chemoresistance and tumorigenesis in recipient tumor cells and to elucidate the underlying mechanism in vivo and in vitro. Microarray and qRT-PCR assays demonstrated that miRNA-205 was upregulated in tamoxifen resistance MCF-7/TAMR-1 (M/T) cells and M/T cell-derived exosomes (M/T-Exo). The M/T-Exo was internalized by human BC cells (BCCs), causing increased expression of miRNA-205 in BCCs. Coculturing with M/T-Exo promoted tamoxifen resistance, proliferation, migration, and invasion while suppressed apoptosis in recipient BCCs, which were associated with activating the caspase pathway and phosphorylating Akt. Luciferase reporter assays showed that miRNA-205 directly targeted E2F Transcription Factor 1 (E2F1) in BCCs. Furthermore, knockdown of miRNA-205 or overexpression of E2F1 reversed the roles of M/T-Exo in BCCs. In vivo experiments showed that the intratumoral injection of M/T-Exo caused greater tamoxifen resistance and larger tumor size relative to mice treated with miRNA-205-knockdown or E2F1-overexpressing BCCs. Together, the results suggest that exosomal miRNA-205 may promote tamoxifen resistance and tumorigenesis in BC through targeting E2F1 in vivo and in vitro.
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