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A Novel circ_0104345/miR-876-3p/ZBTB20 Axis Regulates the Proliferation, Migration, Invasion, and Apoptosis of Breast Cancer Cells

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Abstract

Breast cancer (BC) is one of the most common malignant tumors in women. CircRNA/miRNA/mRNA regulatory axes have been shown to be involved in the pathogenesis of BC. Here, we sought to analyze the functional mechanism of circ_0104345 in BC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circ_0104345, miR-876-3p and zinc finger and BTB domain containing 20 (ZBTB20) mRNA. Cell Counting Kit-8 (CCK8) and 5–ethynyl–2’–deoxyuridine (EdU) assays were used to test cell viability and proliferation, respectively. Cell migration was tested by wound healing assay, and cell invasion was examined by transwell assay. Tube formation ability was tested by angiogenesis assay. Flow cytometry was applied for cell apoptosis. Western blot assay was utilized to measure the protein expression. The relationship between miR-876-3p and circ_0104345 or ZBTB20 was identified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenografts in mice were conducted to analyze the effect of sh-circ_0104345 on tumor growth in vivo. Circ_0104345 and ZBTB20 were upregulated and miR-876-3p expression was decreased in BC. Circ_0104345 knockdown inhibited cell proliferation, migration, invasion, and enhanced cell apoptosis. MiR-876-3p was targeted by circ_0104345. MiR-876-3p depletion reversed the effects of circ_0104345 downregulation on the progression of BC cells. ZBTB20 was regulated by circ_0104345 through miR-876-3p. The effects of miR-876-3p on BC cell behaviors were restored by ZBTB20 increase. The results of in vivo experiments indicated that silencing of circ_0104345 blocked the growth of xenograft tumors. In this study, we demonstrated, for the first time, the crucial regulation of the new circ_0104345/miR-876-3p/ZBTB20 axis in the biological phenotypes of BC cells.

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Data Availability

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

References

  • Dou D, Ren X, Han M, Xu X, Ge X, Gu Y et al (2021) Circ_0008039 supports breast cancer cell proliferation, migration, invasion, and glycolysis by regulating the miR-140-3p/SKA2 axis. Mol Oncol 15(2):697–709

    Article  CAS  PubMed  Google Scholar 

  • Fan D, Qiu B, Yang XJ, Tang HL, Peng SJ, Yang P et al (2020) LncRNA SNHG8 promotes cell migration and invasion in breast cancer cell through miR-634/ZBTB20 axis. Eur Rev Med Pharmacol Sci 24(22):11639–11649

    CAS  PubMed  Google Scholar 

  • Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L et al (2018) Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis 5(2):77–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J, Yu S, Ding L, Ma L, Chen H, Zhou H et al (2021) The Dual Role of Circular RNAs as miRNA Sponges in Breast Cancer and Colon Cancer. Biomedicines 9(11):1590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J (2019) The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 20(11):675–691

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Jiang B, He Z, Zhu H, He R, Fan S et al (2020) circIQCH sponges miR-145 to promote breast cancer progression by upregulating DNMT3A expression. Aging (albany NY) 12(15):15532–15545

    Article  CAS  PubMed  Google Scholar 

  • Liang X, Liu X, Song Z, Zhu J, Zhang J (2022) Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p. Clin Exp Pharmacol Physiol 49(12):1257–1269

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Cai GX, Zhai XM, Yang XX, Li M, Li K et al (2021) Plasma-Derived Extracellular Vesicles Circular RNAs Serve as Biomarkers for Breast Cancer Diagnosis. Front Oncol 11:752651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Jiang J, Hui X, Wang W, Fang D, Ding L (2018) Mir-758-5p Suppresses Glioblastoma Proliferation, Migration and Invasion by Targeting ZBTB20. Cell Physiol Biochem 48(5):2074–2083

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  • Lou W, Ding B, Wang J, Xu Y (2020) The Involvement of the hsa_circ_0088494-miR-876-3p-CTNNB1/CCND1 Axis in Carcinogenesis and Progression of Papillary Thyroid Carcinoma. Front Cell Dev Biol 8:605940

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma HR, Mu WB, Zhang KY, Zhou HK, Jiang RD, Cao L (2020) CircVCAN regulates the proliferation and apoptosis of osteoarthritis chondrocyte through NF-kappaB signaling pathway. Eur Rev Med Pharmacol Sci 24(12):6517–6525

    PubMed  Google Scholar 

  • Pan G, Mao A, Liu J, Lu J, Ding J, Liu W (2020) Circular RNA hsa_circ_0061825 (circ-TFF1) contributes to breast cancer progression through targeting miR-326/TFF1 signalling. Cell Prolif 53(2):e12720

    Article  PubMed  PubMed Central  Google Scholar 

  • Peterson ML, Ma C, Spear BT (2011) Zhx2 and Zbtb20: novel regulators of postnatal alpha-fetoprotein repression and their potential role in gene reactivation during liver cancer. Semin Cancer Biol 21(1):21–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu J, Peng P, Xin M, Wen Z, Chen Z, Lin S et al (2020) ZBTB20-mediated titanium particle-induced peri-implant osteolysis by promoting macrophage inflammatory responses. Biomater Sci 8(11):3147–3163

    Article  CAS  PubMed  Google Scholar 

  • Sengupta D, Deb M, Kar S, Pradhan N, Parbin S, Kirtana R et al (2021) Dissecting miRNA facilitated physiology and function in human breast cancer for therapeutic intervention. Semin Cancer Biol 72:46–64

    Article  CAS  PubMed  Google Scholar 

  • Shen Y, Zhang M, Da L, Huang W, Zhang C (2020) Circular RNA circ_SETD2 represses breast cancer progression via modulating the miR-155-5p/SCUBE2 axis. Open Med (wars) 15(1):940–953

    Article  CAS  PubMed  Google Scholar 

  • Shyu AB, Wilkinson MF, van Hoof A (2008) Messenger RNA regulation: to translate or to degrade. EMBO J 27(3):471–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71(3):209–249

    Article  PubMed  Google Scholar 

  • Wang H, Wei Z, Li H, Guan Y, Han Z, Wang H et al (2020) MiR-377-3p inhibits atherosclerosis-associated vascular smooth muscle cell proliferation and migration via targeting neuropilin2. Biosci Rep 40(6):BSR20193425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu D, Jia H, Zhang Z, Li S (2021) Circ-PRMT5 promotes breast cancer by the miR-509-3p/TCF7L2 axis activating the PI3K/AKT pathway. J Gene Med 23(2):e3300

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Xie Q, Xie M, Zeng Y, Liu Q (2021) LncRNA SNHG8 Serves as an oncogene in breast cancer through miR-634/ZBTB20 Axis. Cancer Manag Res 13:3017–3028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Shen P, Yao T, Ma J, Chen Z, Zhu J et al (2021) Novel role of circRSU1 in the progression of osteoarthritis by adjusting oxidative stress. Theranostics 11(4):1877–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu H, Dong L, Wang H, Zhang Y, Wang Z, Wang C et al (2021) LINC00504 promotes the malignant biological behavior of breast cancer cells by upregulating HMGB3 via decoying MICRORNA-876-3p. Cancer Manag Res 13:1803–1815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan M, Zhang J, He Y, Yi G, Rong L, Zheng L et al (2022) Circ_0062558 promotes growth, migration, and glutamine metabolism in triple-negative breast cancer by targeting the miR-876-3p/SLC1A5 axis. Arch Gynecol Obstet 306(5):1643–1655

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z (2020) Silencing LINC00504 inhibits cell proliferation, invasion as well as migration and promotes cell apoptosis in lung cancer cells via upregulating miR-876-3p. Cytotechnology 72(6):807–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Xie Z, Zhou L, Li L, Zhang H, Zhou G et al (2012) The zinc finger protein ZBTB20 regulates transcription of fructose-1,6-bisphosphatase 1 and β cell function in mice. Gastroenterology 142(7):1571-1580.e1576

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Shi JH, Jiang H, Wang K, Lu JY, Jiang X et al (2018) ZBTB20 regulates EGFR expression and hepatocyte proliferation in mouse liver regeneration. Cell Death Dis 9(5):462

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhou X, Zhang M, Cheng L, Zhang Y, Wang X (2019) ZBTB20 promotes cell migration and invasion of gastric cancer by inhibiting IkappaBalpha to induce NF-kappaB activation. Artif Cells Nanomed Biotechnol 47(1):3862–3872

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Bai X, Zeng X, Liu J, Liu F, Zhang Z (2021) circRNA-miRNA-mRNA in breast cancer. Clin Chim Acta 523:120–130

    Article  CAS  PubMed  Google Scholar 

  • Zhao ZJ, Shen J (2017) Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol 14(5):514–521

    Article  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

H.C. designed and supervised the study. H.W. and A.W.conducted the experiments and drafted the manuscript. L.W. and F.S.collected and analyzed the data. F.L. operated the software and edited the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Hengfeng Cui.

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Competing interests

The authors declare that they have no conflict of interest.

Ethical Approval

All patients gave informed consent, and the present study was conducted with the approval of the Ethics Committee of Third People’s Hospital of Yancheng.

Consent to Participate

All patients gave informed consent, and the present study was conducted with the approval of the Ethics Committee of Third People’s Hospital of Yancheng.

Research Involving Human and Animal Rights

The Animal Welfare and Research Ethics Committee of Third People’s Hospital of Yancheng approved the animal experiments.

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Supplementary Information

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10528_2023_10391_MOESM1_ESM.tif

Supplementary file1 (TIF 23228 KB)—Supplementary Fig. 1 Images of cell migration assay, invasion assay, tube formation assay, and apoptosis assay in Figure 4D-4G

10528_2023_10391_MOESM2_ESM.tif

Supplementary file2 (TIF 22642 KB)— Supplementary Fig. 2 Images of cell migration assay, invasion assay, tube formation assay, and apoptosis assay in Figure 6D-6G

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Wu, H., Wang, A., Wang, L. et al. A Novel circ_0104345/miR-876-3p/ZBTB20 Axis Regulates the Proliferation, Migration, Invasion, and Apoptosis of Breast Cancer Cells. Biochem Genet 61, 2548–2565 (2023). https://doi.org/10.1007/s10528-023-10391-z

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  • DOI: https://doi.org/10.1007/s10528-023-10391-z

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