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Circ_CSPP1 Regulates the Development of Non-small Cell Lung Cancer via the miR-486-3p/BRD9 Axis

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Abstract

In this study, we explored the role of circ_CSPP1 in non-small cell lung cancer (NSCLC) using NSCLC cell lines (A549 and H1299) and human bronchial epithelioid cells (16HBE). The differential expression of circ_CSPP1, miR-486-3p and BRD9 in NSCLC by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot in A549 cells, H1299 cells, 16HBE cells, NSCLC tissues and healthy lung tissues. Dual-luciferase reporter assay was conducted to verify the interaction between circ_CSPP1 and miR-486-3p or miR-486-3p and BRD9. The effect of circ_CSPP1/miR-486-3p/BRD9 axis on NSCLC cell proliferation was evaluated using cell counting kit-8 assay, colony formation assay, and 5-ethynyl-2′-deoxyuridine assay. Additionally, transwell assays were performed to evaluate the effect of circ_CSPP1/miR-486-3p/BRD9 axis on A549 and H1299 cell migration and invasion. The effect of circ_CSPP1 on tumor tumorigenesis of A549 cells in vivo was determined by xenograft tumor model and immunohistochemistry assay. Circ_CSPP1 and BRD9 expression were upregulated, while miR-486-3p expression was downregulated in tumor tissues of NSCCL patients and A549 and H1299 cells. Circ_CSPP1 specifically bound miR-486-3p, and miR-486-3p could target BRD9. Circ_CSPP1 upregulation promoted proliferation, invasion and migration of NSCLC cells, circ_CSPP1 knockdown or miR-486-3p upregulation had the opposite effects. Circ_CSPP1 knockdown-induced effects were reverted by miR-486-3p inhibition. Similarly, the effects of miR-486-3p upregulation on NSCLC cell proliferation, invasion and migration were reversed by BRD9 overexpression. In addition, circ_CSPP1 silencing inhibited tumor growth in nude mice. Circ_CSPP1 promoted A549 and H1299 cell malignancy by competitively inhibiting BRD9 and binding to miR-486-3p.

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Acknowledgements

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Funding

This study doesn’t receive any financial support as well as any role of funding bodies.

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Author notes

  1. Dan Xie and Shuyi Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Huizhou Municipal Central Hospital of Guangdong Province, No. 41, North Eling Road, Huizhou, 516000, Guangdong, People’s Republic of China

    Dan Xie, Shuyi Zhang, Weizhen Huang, Ying He, Yi Li & Hailin Xiong

  2. Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital of Guangdong Province, Huizhou, Guangdong, People’s Republic of China

    Xiaocong Jiang

  3. Department of Neurology, Huizhou Municipal Central Hospital of Guangdong Province, Huizhou, Guangdong, People’s Republic of China

    Sihan Chen

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  1. Dan Xie
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10528_2022_10231_MOESM1_ESM.tif

Figure S1 Transfection efficiency of sh-circ_CSPP1 and circ_CSPP1 in A549 and H1299 cells. (A-B) The transfection efficiency of sh-circ_CSPP1 and circ_CSPP1 in A549 and H1299 cells was detected by qRT-PCR. Data were obtained from three independent and not replicated experiments. *P < 0.05. Supplementary file1 (TIF 98 kb)

10528_2022_10231_MOESM2_ESM.tif

Figure S2 The expression analysis of miRNAs and mRNAs. (A) The expression of the first six miRNAs with high circ_CSPP1-binding ability in circ_CSPP1-depleted A549 cells was detected by qRT-PCR. (B) The expression of mRNAs containing miR-486-3p-binding sites and participating in NSCLC progression after miR-486-3p overexpression was checked by qRT-PCR in A549 cells. Data were obtained from three independent and not replicated experiments.*P < 0.05. Supplementary file2 (TIF 339 kb)

10528_2022_10231_MOESM3_ESM.tif

Figure S3 The schematic illustration showing the mechanism by which circ_CSPP1 regulated NSCLC cell proliferation, migration and invasion. Supplementary file3 (TIF 166 kb)

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Xie, D., Zhang, S., Jiang, X. et al. Circ_CSPP1 Regulates the Development of Non-small Cell Lung Cancer via the miR-486-3p/BRD9 Axis. Biochem Genet 61, 1–20 (2023). https://doi.org/10.1007/s10528-022-10231-6

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