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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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
[1] Harrod A, Lai CF, Goldsbrough I, et al. Genome engineering for estrogen receptor mutations reveals differential responses to anti-estrogens and new prognostic gene signatures for breast cancer [J]. Oncogene, 2022. doi:0.1038/s41388-022-02483-8.
[2] Battisti NML, Smith IE. Preventing late recurrence in hormone receptor-positive early breast cancer: a review [J]. Eur J Cancer, 2022, 172: 53-64. doi: 10.1016/j.ejca.2022.05.028.
[3] Jeffreys SA, Powter B, Balakrishnar B, et al. Endocrine resistance in breast cancer: the role of estrogen receptor stability [J]. Cells, 2020, 9(9): 2077. doi: 10.3390/cells9092077.
[4] Chen B, Dragomir MP, Yang C, et al. Targeting non-coding RNAs to overcome cancer therapy resistance [J]. Signal Transduct Target Ther, 2022, 7(1): 121. doi: 10.1038/s41392-022-00975-3.
[5] 刘岩, 张曼, 姜朝阳, 等. LncRNA-HOTAIR调控H3K27me3影响巨噬细胞迁移的机制[J]. 山东大学学报(医学版), 2022, 60(6): 1-9. LIU Yan, ZHANG Man, JIANG Chaoyang, et al. Mechanism of LncRNA-HOTAIR regulating macrophage migration through modulating H3K27me3 [J]. Journal of Shandong University(Health Sciences), 2022, 60(6): 1-9.
[6] Lin X, Dinglin X, Cao S, et al. Enhancer-driven lncRNA BDNF-AS induces endocrine resistance and malignant progression of breast cancer through the RNH1/TRIM21/mTOR cascade [J]. Cell Rep, 2020, 31(10): 107753. doi: 10.1016/j.celrep.2020.107753.
[7] Barazetti JF, Jucoski TS, Carvalho TM, et al. From micro to long: non-coding RNAs in tamoxifen resistance of breast cancer cells [J]. Cancers(Basel), 2021, 13(15): 3688. doi: 10.3390/cancers13153688.
[8] Zhang H, Zhang J, Dong L, et al. LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer [J]. Open Med(Wars), 2021, 16(1): 68-80.
[9] Shi Q, Li Y, Li S, et al. LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer [J]. Nat Commun, 2020, 11(1): 5513. doi: 10.1038/s41467-020-19349-w.
[10] Saha T, Lukong KE. Breast cancer stem-like cells in drug resistance: a review of mechanisms and novel therapeutic strategies to overcome drug resistance [J]. Front Oncol, 2022, 12: 856974. doi: 10.3389/fonc.2022.856974.
[11] Mao XD, Wei X, Xu T, et al. Research progress in breast cancer stem cells: characterization and future perspectives [J]. Am J Cancer Res, 2022, 12(7): 3208-3222.
[12] Xu H, Zhang F, Gao X, et al. Fate decisions of breast cancer stem cells in cancer progression [J]. Front Oncol, 2022, 12: 968306. doi: 10.3389/fonc.2022.968306.
[13] Ibragimova M, Tsyganov M, Litviakov N. Tumour stem cells in breast cancer [J]. Int J Mol Sci, 2022, 23(9): 5058. doi: 10.3390/ijms23095058.
[14] Alataki A, Dowsett M. Human epidermal growth factor receptor-2 and endocrine resistance in hormone-dependent breast cancer [J]. Endocr Relat Cancer, 2022, 29(8): R105-R122.
[15] Dong C, Wu J, Chen Y, et al. Activation of PI3K/AKT/mTOR pathway causes drug resistance in breast cancer [J]. Front Pharmacol, 2021, 12: 628690. doi: 10.3389/fphar.2021.628690.
[16] Azuma K, Ikeda K, Suzuki T, et al. TRIM47 activates NF-kappaB signaling via PKC-epsilon/PKD3 stabilization and contributes to endocrine therapy resistance in breast cancer [J]. Proc Natl Acad Sci USA, 2021, 118(35): e2100784118. doi: 10.1073/pnas.2100784118.
[17] Shi X, Yang J, Deng S, et al. TGF-beta signaling in the tumor metabolic microenvironment and targeted therapies [J]. J Hematol Oncol, 2022, 15(1): 135. doi: 10.1186/s13045-022-01349-6.
[18] Takahashi K, Podyma-Inoue KA, Saito M, et al. TGF-beta generates a population of cancer cells residing in G1 phase with high motility and metastatic potential via KRTAP2-3 [J]. Cell Rep, 2022, 40(13): 111411. doi: 10.1016/j.celrep.2022.111411.
[19] Maslankova J, Vecurkovska I, Rabajdova M, et al. Regulation of transforming growth factor-beta signaling as a therapeutic approach to treating colorectal cancer [J]. World J Gastroenterol, 2022, 28(33): 4744-4761.
[20] 刘群, 李丽娜, 刘健, 等. 卵巢癌SOX4介导TGF-β1诱导的上皮间质转化对侵袭转移能力的影响 [J]. 首都医科大学学报, 2022, 43(3): 336-342. LIU Qun, LI Lina, LIU Jian, et al. Effect of SOX4-mediated TGF-β1-induced epithelial-mesenchymal transition on invasion and metastasis in ovarian cancer [J]. Journal of Capital Medical University, 2022, 43(3): 336-342.
[21] Peng P, Zhu H, Liu D, et al. TGFBI secreted by tumor-associated macrophages promotes glioblastoma stem cell-driven tumor growth via integrin alphavbeta5-Src-Stat3 signaling [J]. Theranostics, 2022, 12(9): 4221-4236.
[22] Thambyrajah R, Monteiro R. In the spotlight: the role of TGFbeta signalling in haematopoietic stem and progenitor cell emergence [J]. Biochem Soc Trans, 2022, 50(2): 703-712.
[23] Garcia-Gomez P, Golan I, Dadras MS, et al. NOX4 regulates TGFbeta-induced proliferation and self-renewal in glioblastoma stem cells [J]. Mol Oncol, 2022, 16(9): 1891-1912.
[24] Zhang Z, Xu Y. FZD7 accelerates hepatic metastases in pancreatic cancer by strengthening EMT and stemness associated with TGF-beta/SMAD3 signaling [J]. Mol Med, 2022, 28(1): 82. doi: 10.1186/s10020-022-00509-1.
[25] Wang B, Cao C, Liu X, et al. BRCA1-associated protein inhibits glioma cell proliferation and migration and glioma stem cell self-renewal via the TGF-beta/PI3K/AKT/mTOR signalling pathway [J]. Cell Oncol(Dordr), 2020, 43(2): 223-235.
[26] Rodrigues-Junior DM, Tsirigoti C, Lim SK, et al. Extracellular vesicles and transforming growth factor beta signaling in cancer [J]. Front Cell Dev Biol, 2022, 10: 849938. doi: 10.3389/fcell.2022.849938.
[27] Chan MK, Chung JY, Tang PC, et al. TGF-beta signaling networks in the tumor microenvironment [J]. Cancer Lett, 2022, 550:215925. doi: 10.1016/j.canlet.2022.215925.
[28] Wang Z, Chen J, Wang S, et al. RGS6 suppresses TGF-beta-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4 [J]. Cell Death Dis, 2022, 13(7): 656. doi: 10.1038/s41419-022-05093-0.
[29] Zou ML, Chen ZH, Teng YY, et al. The Smad dependent TGF-beta and BMP signaling pathway in bone remodeling and therapies [J]. Front Mol Biosci, 2021, 8: 593310. doi: 10.3389/fmolb.2021.593310.
[30] Aykul S, Maust J, Thamilselvan V, et al. Smad2/3 activation regulates Smad1/5/8 signaling via a negative feedback loop to inhibit 3T3-L1 adipogenesis [J]. Int J Mol Sci, 2021, 22(16): 8472. doi: 10.3390/ijms22168472.
[31] Tzavlaki K, Moustakas A. TGF-beta signaling [J]. Biomolecules, 2020, 10(3): 487. doi: 10.3390/biom10030487.
[32] Song X, Wei C, Li X. The signaling pathways associated with breast cancer bone metastasis [J]. Front Oncol, 2022, 12: 855609. doi: 10.3389/fonc.2022.855609.
[33] Chen X, Yan N. Stachydrine inhibits TGF-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma cells through the TGF-beta/Smad and PI3K/Akt/mTOR signaling pathways[J]. Anticancer Drugs, 2021, 32(8): 786-792.
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