机构:[1]Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Guangdong, Peoples R China[2]Sun Yat Sen Univ, Affiliated Hosp 5, Zhuhai, Guangdong, Peoples R China[3]First Peoples Hosp Changde City, Dept Pathol, Changde, Hunan, Peoples R China[4]Chengdu Univ Tradit Chinese Med, State Key Lab Southwestern Chinese Med Resources, Chengdu, Sichuan, Peoples R China
Breast cancer (BC) is the most common cancer and the top cause of female mortality worldwide. The prognosis for patients with breast cancer liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated with the progression of BC. Exploration of circRNAs presents a promising avenue for identifying metastasis-targeting agents and improving the prognosis of patients with BCLM. Microarray and bioinformatic analyses were used to analyze differentially expressed circRNAs between three pairs of BCLM and primary BC. The roles of hsa_circ_0060467 (circMYBL2) and its target gene E2F1 in BC cells were explored by multiple functional experiments. And xenograft mouse models and hepatic metastases of BC hemi-spleen models were used to illustrate the function of circMYBL2 in vivo. The intrinsic molecular mechanism involving circMYBL2 was confirmed by bioinformatics analyses, RIP assays, CHIRP assays, luciferase reporter assays, and rescue experiments. CircMYBL2 was overexpressed in BCLM tissues and BC cells. Functionally, circMYBL2 can facilitate the proliferation and liver metastasis of BC. Mechanistically, circMYBL2 upregulated the transcription factor E2F1 by sponging miR-1205 and complexing with eukaryotic translation initiation factor 4A3 (eIF4A3) and then facilitated the epithelial-mesenchymal transition (EMT) process in BC cells. Our findings showed that circMYBL2 promoted the tumorigenesis and aggressiveness of BC through the circMYBL2/miR-1205/E2F1 and circMYBL2/eIF4A3/E2F1 axes, which may provide a novel targeted therapy for patients with BCLM.
基金:
Science and Technology Program of Guangzhou [202103000020]; Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China
第一作者机构:[1]Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou, Guangdong, Peoples R China[2]Sun Yat Sen Univ, Affiliated Hosp 5, Zhuhai, Guangdong, Peoples R China
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通讯作者:
推荐引用方式(GB/T 7714):
Zeng Yan,Du Wei,Huang Zhongying,et al.Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205[J].CELL DEATH DISCOVERY.2023,9(1):doi:10.1038/s41420-023-01448-4.
APA:
Zeng, Yan,Du, Wei,Huang, Zhongying,Wu, Song,Ou, Xueqi...&Tang, Hailin.(2023).Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205.CELL DEATH DISCOVERY,9,(1)
MLA:
Zeng, Yan,et al."Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205".CELL DEATH DISCOVERY 9..1(2023)