期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 26, 期 -, 页码 122-134出版社
CELL PRESS
DOI: 10.1016/j.omtn.2021.07.003
关键词
-
资金
- National Natural Science Foundation of China [82073204]
- Shanghai Municipal Health Commission [202040157]
This study reveals the crucial role of hsa_circ_0068631 in breast cancer, showing that it regulates tumor biological activities by influencing the expression and stability of c-Myc. The findings provide a new target for breast cancer treatment.
Breast cancer (BC) is one of the most common malignancies among women worldwide with a high incidence of recurrence and metastasis. In this study, we demonstrate that hsa_ circ_0068631, a circRNA generated from the transferrin receptor (TFRC), is upregulated in BC tissues and cell lines. Knockdown of hsa_circ_0068631 inhibited the proliferation and migration of BC cells in vitro and in vivo. Mechanistically, an RNA pull-down assay and RNA immunoprecipitation assay revealed that eukaryotic translation initiation factor 4A3 (EIF4A3) could bind to hsa_circ_0068631 and c-Myc mRNA. Additionally, the expression of hsa_circ_0068631 was positively correlated with c-Myc, and the upregulation of hsa_ circ_0068631 was a crucial factor for the dysregulation of c-Myc. Through an actinomycin D assay, we confirmed that the mRNA stability of c-Myc was influenced by hsa_circ_0068631 and EIF4A3. Furthermore, hsa_circ_0068631 could recruit EIF4A3 to increase c-Myc mRNA stability. Rescue assays manifesting depletion of c-Myc rescued the promotive effect of hsa_circ_0068631 overexpression on biological activities in BC. In conclusion, to our knowledge, this study is the first to unveil the role of hsa_circ_0068631 and the hsa_ circ_0068631/EIF4A3/c-Myc axis in BC, providing a new target for BC treatment.
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