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Circ_0008673 regulates breast cancer malignancy by miR-153-3p/CFL2 axis

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway.

Methods

The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo.

Results

Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo.

Conclusion

Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.

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Authors and Affiliations

Authors

Contributions

LZ, WZ, XC conceived and designed the experiments; ZZ and JT performed the experiments, Funding acquisition; YS and FC contributed reagents/materials/analysis tools; XY wrote the paper, SL revised the paper All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Shan Liu or Xiaojun Cai.

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Conflict of interest

The authors declare that they have no financial conflicts of interest.

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Supplementary Information

Below is the link to the electronic supplementary material.

404_2021_6149_MOESM1_ESM.tif

Supplementary file1 Fig. S1 Identification of location and stability of circ_0008673 in MCF-10AT and MCF-7 cells. A and B Cytoplasmic and nuclear circ_0008673 analysis assay was employed to demonstrate that circ_0008673 was chiefly located in cytoplasm of MCF-10AT and MCF-7 cells. C and D RNase R resistance analysis assay was used to assess the stability of circ_0008673. ***P < 0.001 (TIF 316 KB)

404_2021_6149_MOESM2_ESM.tif

Supplementary file2 Fig. S2 The expression of circ_0008673, miR-153-3p and CFL2 was detected by qRT-PCR or western blot in MCF-10AT or MCF-7. A and B The efficiency of circ_0008673, si-circ_0008673#1 and si-circ_0008673#2 in increasing or decreasing circ_0008673 expression was detected by qRT-PCR in MCF-10AT or MCF-7 cells. C MiR-153-3p expression was detected by qRT-PCR. D The effects of miR-153-3p inhibitors and mimics on miR-153-3p expression were detected by qRT-PCR in MCF-10AT or MCF-7 cells. E The efficiency of si-CFL2 and CFL2 in affecting CFL2 expression was determined by western blot assay in MCF-10AT or MCF-7 cells. ***P < 0.001 (TIF 438 KB)

404_2021_6149_MOESM3_ESM.tif

Supplementary file3 Fig. S3 Circ_0008673 silencing repressed breast cancer cell malignancy. A The effect of circ_0008673 silencing on cell viability was revealed by CCK-8 assay in MCF-7 cells. B Cell colony-formation assay was employed to determine the impact of circ_0008673 silencing on cell colony-forming ability in MCF-7 cells. C Flow cytometry analysis was employed to analyze the effect of circ_0008673 silencing on cell apoptosis in MCF-7 cells. D and E The effects of circ_0008673 silencing on cell migration and invasion were presented by transwell assay in MCF-7 cells. F The effects of circ_0008673 silencing on the protein expression of E-cadherin and N-cadherin were presented by western blot analysis in MCF-7 cells. **P < 0.01 and ***P < 0.001. (TIF 4681 KB)

404_2021_6149_MOESM4_ESM.tif

Supplementary file4 Fig. S4 Circ_0008673 depletion inhibited cell malignancy of breast cancer by interacting with miR-153-3p. AF MCF-7 cells were severally transfected with si-con, si-circ_0008673#2, si-circ_0008673#2+in-miR-NC and si-circ_0008673#2+in-miR-153-3p. A Cell viability was detected by CCK-8 assay. B Cell colony-forming ability was determined by cell colony-formation assay. C Cell apoptosis was demonstrated by flow cytometry analysis. D and E The migration and invasion of MCF-7 cells were detected by transwell assay. F The protein expression of E-cadherin and N-cadherin was detected by western blot analysis. **P < 0.01 and ***P < 0.001 (TIF 585 KB)

404_2021_6149_MOESM5_ESM.tif

Supplementary file5 Fig. S5 MiR-153-3p mimics inhibited cell proliferation, migration and invasion, whereas promoted cell apoptosis by binding to CFL2. AF MCF-7 cells were transfected with miR-NC, miR-153-3p, miR-153-3p+pcDNA and miR-153-3p+CFL2, respectively. A Cell viability was determined by CCK-8 assay. B Cell colony-forming ability was detected by cell colony-formation assay. C Cell apoptosis was analyzed by flow cytometry analysis. D and E Cell migratory and invasive ability were determined by transwell assay. F The protein levels of E-cadherin and N-cadherin were determined by western blot analysis. ***P < 0.001 (TIF 545 KB)

404_2021_6149_MOESM6_ESM.tif

Supplementary file6 Fig. S6 Circ_0008673 regulated CFL2 expression by associating with miR-153-3p. A The effects between circ_0008673 overexpression and miR-153-3p mimics on CFL2 protein expression were determined by western blot analysis in MCF-10AT cells. B The impacts between circ_0008673 silencing and miR-153-3p inhibitors on CFL2 protein expression were revealed by western blot analysis in MCF-7 cells. ***P < 0.001 (TIF 230 KB)

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Zhang, L., Zhang, W., Zuo, Z. et al. Circ_0008673 regulates breast cancer malignancy by miR-153-3p/CFL2 axis. Arch Gynecol Obstet 305, 223–232 (2022). https://doi.org/10.1007/s00404-021-06149-w

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  • DOI: https://doi.org/10.1007/s00404-021-06149-w

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