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Circ_0000442 functions as a tumor repressor in breast cancer by impacting miR-1229-3p and upregulating ZBTB1

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Abstract

A variety of circular RNAs (circRNAs) have tumor-regulatory roles in breast cancer (BC). Circ_0000442 was reported to inhibit the progression of BC, and this study was designed to explore the novel functional mechanism of circ_0000442 in BC. The expression analysis for circ_0000442, microRNA-1229-3p (miR-1229-3p) and zinc finger and BTB domain containing 1 (ZBTB1) was performed using the quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter assay was used to affirm the target interaction. Cell proliferation was examined using Edu assay and colony formation assay. Cell migration and invasion were assessed by transwell assay. Flow cytometry was applied for the detection of cell apoptosis. Glycolysis was analyzed using the detection kits to measure the glucose consumption and lactate production. The protein expression levels were determined by western blot. The role of circ_0000442 in BC in vivo was explored using tumor xenograft assay. Circ_0000442 expression was downregulated and miR-1229-3p expression was upregulated in BC tissues and cells. Circ_0000442 directly interacted with miR-1229-3p. Circ_0000442 repressed proliferation, migration, invasion and glycolysis but promoted apoptosis in BC cells. The anti-tumor role of circ_0000442 was attributed to the sponge effect on miR-1229-3p. ZBTB1 was a downstream target for miR-1229-3p. Downregulation of miR-1229-3p blocked the malignant behaviors in BC cells by elevating the expression of ZBTB1. Circ_0000442 regulated the ZBTB1 level by targeting miR-1229-3p, and it inhibited tumor growth of BC in vivo by mediating the miR-1229-3p/ZBTB1 axis. All evidence unraveled that circ_0000442 impeded the progression of BC by sponging miR-1229-3p to evoke the ZBTB1 expression upregulation.

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Data availability

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

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Authors and Affiliations

  1. Medical Department, Queen Mary School, Nanchang University, Nanchang, Jiangxi, People’s Republic of China

    Jingyu Liu

  2. Department of Oncology, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Dondhu District, Nanchang, 330006, Jiangxi, People’s Republic of China

    Jianhui Liu

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  1. Jingyu Liu
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Correspondence to Jianhui Liu.

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The present study was approved by the ethical review committee of The Second Affiliated Hospital of Nanchang University. Written informed consent was obtained from all enrolled patients.

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Liu, J., Liu, J. Circ_0000442 functions as a tumor repressor in breast cancer by impacting miR-1229-3p and upregulating ZBTB1. Mamm Genome 33, 543–554 (2022). https://doi.org/10.1007/s00335-022-09950-3

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  • DOI: https://doi.org/10.1007/s00335-022-09950-3

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