Abstract
Endometrial cancer (EC) is the most common gynecological tumor. Circular RNAs are a novel type of non-coding RNA that have important regulatory functions, particularly in the pathogenic progression of cancer. In this study, we investigated the function of circCCL22, and elucidated its molecular mechanism in EC progresssion. The expression of circCCL22, miR-543 and CDC25A in EC tissues and cells were determined by qRT-PCR and western blot. Cell counting kit-8, 5-ethynyl-2′-deoxyuridine, wound healing and transwell assays were executed to assess the cell viability, proliferation, migration and invasion. Dual-luciferase report assay was utilized to investigate the interaction of miR-543 with circCCL22 and CDC25A. The role of circCCL22 in EC in vivo was investigated by xenograft assay. CircCCL22 was notably upregulated in EC tissues and cells. Functionally, circCCL22 knockdown suppressed EC cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. Mechanistically, circCCL22 acted as “miR-543 sponges” to regulate its targeted gene CDC25A expression in EC cells. The inhibiting effect induced by circCCL22 knockdown on EC cell proliferation, migration and invasion was greatly reversed by miR-543 inhibition or CDC25A overexpression. Our results revealed that circCCL22 regulated EC progression through targeting miR-543/CDC25A axis, and it could be a novel therapeutic target of EC.
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References
Makker, V., MacKay, H., Ray-Coquard, I., Levine, D., Westin, S., Aoki, D., et al. (2021). Endometrial cancer. Nature Reviews Disease Primers, 7, 88.
Raglan, O., Kalliala, I., Markozannes, G., Cividini, S., Gunter, M., Nautiyal, J., et al. (2019). Risk factors for endometrial cancer: An umbrella review of the literature. International Journal of Cancer, 145, 1719–1730.
Wang, Y., Lu, T., Wang, Q., Liu, J., & Jiao, W. (2018). Circular RNAs: Crucial regulators in the human body (review). Oncology Reports, 40, 3119–3135.
Li, S., & Han, L. (2019). Circular RNAs as promising biomarkers in cancer: Detection, function, and beyond. Genome Medicine, 11, 15.
Chen, Y., Li, C., Tan, C., & Liu, X. (2016). Circular RNAs: A new frontier in the study of human diseases. Journal of Medical Genetics, 53, 359–365.
Cen, Y., Zhu, T., Zhang, Y., Zhao, L., Zhu, J., Wang, L., et al. (2022). hsa_circ_0005358 suppresses cervical cancer metastasis by interacting with PTBP1 protein to destabilize CDCP1 mRNA. Molecular Therapy-Nucleic Acids, 27, 227–240.
Ji, Y., Yang, S., Yan, X., Zhu, L., Yang, W., Yang, X., et al. (2021). CircCRIM1 promotes hepatocellular carcinoma proliferation and angiogenesis by sponging miR-378a-3p and regulating SKP2 expression. Frontiers in Cell and Developmental Biology, 9, 796686.
Li, C., Li, W., Cao, S., Xu, J., Qian, Y., Pan, X., et al. (2021). Circ_0058106 promotes proliferation, metastasis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through mir-185-3p in hypopharyngeal squamous cell carcinoma. Cell Death and Disease, 12, 1063.
Ye, F., Tang, Q., Ma, F., Cai, L., Chen, M., Ran, X., et al. (2019). Analysis of the circular RNA transcriptome in the grade 3 endometrial cancer. Cancer Management and Research, 11, 6215–6227.
Jin, C., Shi, L., Li, Z., Liu, W., Zhao, B., Qiu, Y., et al. (2019). Circ_0039569 promotes renal cell carcinoma growth and metastasis by regulating miR-34a-5p/CCL22. American Journal of Translational Research, 11, 4935–4945.
Li, T., Xu, J., & Liu, Y. (2021). A Novel Circular RNA CircRFX3 serves as a sponge for MicroRNA-587 in promoting glioblastoma progression via regulating PDIA3. Frontiers in Cell and Developmental Biology, 9, 757260.
Zhou, J., Wang, L., Sun, Q., Chen, R., Zhang, C., Yang, P., et al. (2021). Hsa_circ_0001666 suppresses the progression of colorectal cancer through the miR-576-5p/PCDH10 axis. Clinical and Translational Medicine, 11, e565.
Yang, Q., Yu, B., & Sun, J. (2020). TTK, CDC25A, and ESPL1 as prognostic biomarkers for endometrial cancer. BioMed Research International, 2020, 4625123.
Li, R., Jiang, J., Shi, H., Qian, H., Zhang, X., & Xu, W. (2020). CircRNA: A rising star in gastric cancer. Cellular and Molecular Life Sciences, 77, 1661–1680.
Guo, J., Tong, J., & Zheng, J. (2021). Circular RNAs: A Promising Biomarker for Endometrial Cancer. Cancer Management and Research, 13, 1651–1665.
Liang, Z. Z., Guo, C., Zou, M. M., Meng, P., & Zhang, T. T. (2020). circRNA-miRNA-mRNA regulatory network in human lung cancer: An update. Cancer Cell International, 20, 173.
Liu, Y., Chen, L., Liu, T., Su, X., Peng, L., Chen, J., et al. (2022). Genome-wide circular RNA (circRNA) and mRNA profiling identify a circMET-miR-410-3p regulatory motif for cell growth in colorectal cancer. Genomics, 114, 351–360.
Wang, N., Guo, Y., Song, L., Tong, T., & Fan, X. (2022). Circular RNA intraflagellar transport 80 facilitates endometrial cancer progression through modulating miR-545-3p/FAM98A signaling. Journal of Gynecologic Oncology, 33, e2.
Liu, Y., Chang, Y., & Cai, Y. (2020). Circ_0067835 sponges mir-324-5p to induce HMGA1 expression in endometrial carcinoma cells. Journal of Cellular and Molecular Medicine, 24, 13927–13937.
Jia, Y., Liu, M., & Wang, S. (2020). CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182. Cancer Cell International, 20, 412.
Bing, L., Hong, C., Li-Xin, S., & Wei, G. (2014). MicroRNA-543 suppresses endometrial cancer oncogenicity via targeting FAK and TWIST1 expression. Archives of Gynecology and Obstetrics, 290, 533–541.
Li, R., Hou, S., Zou, M., Ye, K., & Xiang, L. (2021). miR-543 impairs cell proliferation, migration, and invasion in breast cancer by suppressing VCAN. Biochemical and Biophysical Research Communications, 570, 191–198.
Yu, Q., Zhang, Z., He, B., Wang, H., Shi, P., & Li, Y. (2020). MiR-543 functions as tumor suppressor in ovarian cancer by targeting TWIST1. Journal of Biological Regulators and Homeostatic Agents, 34, 101–110.
Su, D. W., Li, X., Chen, J., Dou, J., Fang, G. E., & Luo, C. J. (2020). MiR-543 inhibits proliferation and metastasis of human colorectal cancer cells by targeting PLAS3. European Review for Medical and Pharmacological Sciences, 24, 8812–8821.
Liu, X., Gan, L., & Zhang, J. (2019). miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7. Chemico-Biological Interactions, 302, 83–92.
Chen, S., Tang, Y., Yang, C., Li, K., Huang, X., & Cao, J. (2020). Silencing CDC25A inhibits the proliferation of liver cancer cells by downregulating IL–6 in vitro and in vivo. International Journal of Molecular Medicine, 45, 743–752.
Li, D., Liu, Z., & Ning, G. (2020). Expression of CDC25A in non-small cell lung cancer and its relationship with let-7 gene. Nan Fang Yi Ke Da Xue Xue Bao, 40, 1622–1627.
Ren, K., Wang, W., Sun, S., Wang, D., Liu, X., Hou, X., et al. (2022). Recurrence features and factors influencing post-relapse survival in early-stage endometrial cancer after adjuvant radiotherapy. Journal of Cancer, 13, 202–211.
Liang, X., Zeng, H., Chen, S., Jiang, M., Liu, S., & Fan, J. (2021). Ovarian metastasis risk factors in endometrial carcinoma: A systematic review and meta-analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 267, 245–255.
Babaei, G., Aziz, S. G., & Jaghi, N. Z. Z. (2021). EMT, cancer stem cells and autophagy; the three main axes of metastasis. Biomedicine & Pharmacotherapy, 133, 110909.
Nowak, E., & Bednarek, I. (2021). Aspects of the epigenetic regulation of EMT related to cancer metastasis. Cells, 10, 3435.
Zmarzły, N., Hermyt, E., Kruszniewska-Rajs, C., Gola, J., Witek, A., Mazurek, U., et al. (2021). Expression profile of EMT-related genes and miRNAs involved in signal transduction via the wnt pathway and cadherins in endometrial cancer. Current Pharmaceutical Biotechnology, 22, 1663–1671.
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Liu, S., Wang, M., Lv, X. et al. CircCCL22 Regulates CDC25A via Sponging miR-543 and Promotes Proliferation and Metastasis in Endometrial Cancer. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00876-y
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DOI: https://doi.org/10.1007/s12033-023-00876-y