Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (1): 17-26.doi: 10.6040/j.issn.1671-7554.0.2022.1064

• 基础医学 • Previous Articles    

LncRNA ZNF528-AS1 promotes tamoxifen resistance and progression of breast cancer

ZHANG Jianshu1, ZHANG Hanwen1, ZHAO Wenjing2   

  1. 1. Department of Breast Surgery;
    2. Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2023-01-10

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61

Abstract: Objective To investigate the effects of long non-coding RNA(LncRNA)ZNF528-AS1 on tamoxifen resistance and progression of breast cancer as well as the potential regulatory mechanism. Methods The differentially expressed lncRNAs among tamoxifen-resistant breast cancer cells/xenograft tissues and parent cells/ xenograft tissues were analyzed with RNA-seq high-throughput sequencing technology, and candidate lncRNAs associated with tamoxifen resistance were screened. The expressions of candidate lncRNAs were verified with quantitative real-time PCR(qRT-PCR). Breast cancer cells were transfected with liposomes to construct ZNF528-AS1 overexpression and knockdown cell models. The effects of ZNF528-AS1 on the proliferation, tumor stemness and tamoxifen resistance were detected with MTT, colony formation, mammosphere formation, and EdU assays. The role of ZNF528-AS1 in the metastasis of breast cancer was evaluated with Transwell migration and invasion assays. The downstream regulatory pathways of ZNF528-AS1 were detected with RNA-seq high-throughput sequencing and bioinformatics analysis, and verified with Western blotting and functional experiments. Results The differentially expressed lncRNAs were screened out and verified. ZNF528-AS1 was significantly upregulated in tamoxifen-resistant cells. Overexpression of ZNF528-AS1 in breast cancer cells promoted cell proliferation, colony formation ability, tumor stemness, and tamoxifen resistance. In addition, ZNF528-AS1 overexpression enhanced the migration and invasion abilities of breast cancer cells. ZNF528-AS1 knockdown reduced cell proliferation, tamoxifen resistance, tumor stemness, migration, and invasion. ZNF528-AS1 overexpression might be involved in the regulation of transforming growth factor(TGF-β)signaling pathway. ZNF528-AS1 activated both canonical and non-canonical TGF-β signaling pathways. TGF-β pathway inhibitor SB431542 reversed the proliferation, migration and invasion of breast cancer cells enhanced by ZNF528-AS1 overexpression. Conclusion ZNF528-AS1 can promote tamoxifen resistance and progression of breast cancer, and its mechanism might be related to the activation of TGF-β pathway.

Key words: Breast cancer, ZNF528-AS1, Tamoxifen resistance, Tumor stemness, Progression

CLC Number: 

  • R737.9
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