Abstract
Circular RNA (circRNA) has been confirmed to regulate breast cancer (BC) progression. However, the role of circ_0059457 in BC progression is still unclear.The expression of circ_0059457, taspase 1 (TASP1), microRNA (miR)-140-3p and ubiquitin-binding enzyme E2C (UBE2C) was detected by quantitative real-time PCR. Cell proliferation, migration, invasion and sphere formation ability were assessed by cell counting kit-8 assay, EdU assay, wound healing assay, transwell assay and sphere formation assay. Cell glycolysis was assessed by detecting glucose uptake, lactate levels and ATP/ADP ratio. Dual-luciferase reporter assay, RIP assay, RNA pull-down assay were used to validate RNA interaction. Xenograft tumor model to assess the effect of circ_0059457 on BC tumor growth in vivo. Circ_0059457 had elevated expression in BC tissues and cells. Circ_0059457 knockdown inhibited BC cell proliferation, metastasis, sphere formation ability, and glycolysis. In terms of mechanism, circ_0059457 sponged miR-140-3p, and miR-140-3p targeted UBE2C. MiR-140-3p inhibition reversed the effect of circ_0059457 knockdown on BC cell malignant behaviors. Besides, miR-140-3p overexpression inhibited BC cell proliferation, metastasis, sphere formation ability and glycolysis, and these effects were abrogated by UBE2C enhancement. Furthermore, circ_0059457 regulated UBE2C expression through sponging miR-140-3p. Additionally, circ_0059457 knockdown obviously inhibited BC tumor growth in vivo. Circ_0059457 promoted BC progression via miR-140-3p/UBE2C axis, which provided potential target for the treatment of BC.
Similar content being viewed by others
Data Availability
Not applicable.
References
Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ (2020) Regulatory mechanism of MicroRNA expression in Cancer. Int J Mol Sci. https://doi.org/10.3390/ijms21051723
Anastasiadi Z, Lianos GD, Ignatiadou E, Harissis HV, Mitsis M (2017) Breast cancer in young women: an overview. Updates Surg 69:313–317. https://doi.org/10.1007/s13304-017-0424-1
Braden MA, Stankowski VR, Engel JM, Onitilo AA (2014) Breast cancer biomarkers: risk assessment, diagnosis, prognosis, prediction of treatment efficacy and toxicity, and recurrence. Curr Pharm Des 20:4879–4898. https://doi.org/10.2174/1381612819666131125145517
Cao L, Wang M, Dong Y, Xu B, Chen J, Ding Y, Qiu S, Li L, Karamfilova Zaharieva E, Zhou X, Xu Y (2020) Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1alpha/HK2. Cell Death Dis 11:145. https://doi.org/10.1038/s41419-020-2336-0
Chen L, Shan G (2021) CircRNA in cancer: fundamental mechanism and clinical potential. Cancer Lett 505:49–57. https://doi.org/10.1016/j.canlet.2021.02.004
Chiang AJ, Li CJ, Tsui KH, Chang C, Chang YI, Chen LW, Chang TH, Sheu JJ (2020) UBE2C drives human cervical Cancer progression and is positively modulated by mTOR. Biomolecules. https://doi.org/10.3390/biom11010037
Cui X, Chen J, Zheng Y, Shen H (2020) Circ_0000745 promotes the progression of Cervical Cancer by regulating miR-409-3p/ATF1 Axis. Cancer Biother Radiopharm. https://doi.org/10.1089/cbr.2019.3392
Dastsooz H, Cereda M, Donna D, Oliviero S (2019) A comprehensive bioinformatics analysis of UBE2C in cancers. Int J Mol Sci. https://doi.org/10.3390/ijms20092228
Ding L, Gu H, Xiong X, Ao H, Cao J, Lin W, Yu M, Lin J, Cui Q (2019) MicroRNAs involved in carcinogenesis, prognosis, therapeutic resistance and applications in human triple-negative breast Cancer. Cells. https://doi.org/10.3390/cells8121492
Fahad Ullah M (2019) Breast cancer: current perspectives on the disease status. Adv Exp Med Biol 1152:51–64. https://doi.org/10.1007/978-3-030-20301-6_4
Hombach S, Kretz M (2016) Non-coding RNAs: classification, biology and functioning. Adv Exp Med Biol 937:3–17. https://doi.org/10.1007/978-3-319-42059-2_1
Hu C, Zou Y, Jing LL (2020) Mir-140-3p inhibits progression of non-small cell lung cancer by targeting Janus kinase 1. J Biosci 45:48
Huang A, Zheng H, Wu Z, Chen M, Huang Y (2020) Circular RNA-protein interactions: functions, mechanisms, and identification. Theranostics 10:3503–3517. https://doi.org/10.7150/thno.42174
Jiang W, Li T, Wang J, Jiao R, Shi X, Huang X, Ji G (2019) Mir-140-3p suppresses cell growth and induces apoptosis in colorectal cancer by targeting PD-L1. Onco Targets Ther 12:10275–10285. https://doi.org/10.2147/OTT.S226465
Kristensen LS, Hansen TB, Veno MT, Kjems J (2018) Circular RNAs in cancer: opportunities and challenges in the field. Oncogene 37:555–565. https://doi.org/10.1038/onc.2017.361
Li Y, Ma H (2022) circRNA PLOD2 promotes tumorigenesis and Warburg effect in colon cancer by the miR-513a-5p/SIX1/LDHA axis. Cell Cycle 21:2484–2498. https://doi.org/10.1080/15384101.2022.2103339
Li X, Yang J, Peng L, Sahin AA, Huo L, Ward KC, O’Regan R, Torres MA, Meisel JL (2017) Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat 161:279–287. https://doi.org/10.1007/s10549-016-4059-6
Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W (2020) CircRNA: a rising star in gastric cancer. Cell Mol Life Sci 77:1661–1680. https://doi.org/10.1007/s00018-019-03345-5
Liu Z, Zhou Y, Liang G, Ling Y, Tan W, Tan L, Andrews R, Zhong W, Zhang X, Song E, Gong C (2019) Circular RNA hsa_circ_001783 regulates breast cancer progression via sponging miR-200c-3p. Cell Death Dis 10:55. https://doi.org/10.1038/s41419-018-1287-1
Liu T, Ye P, Ye Y, Lu S, Han B (2020) Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA-328-3p-mediated inhibition of COL1A1. J Cell Mol Med 24:2189–2201. https://doi.org/10.1111/jcmm.14875
Lu ZN, Song J, Sun TH, Sun G (2021) UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway. Chin Med J (Engl) 134:2465–2474. https://doi.org/10.1097/CM9.0000000000001708
Mishra S, Yadav T, Rani V (2016) Exploring miRNA based approaches in cancer diagnostics and therapeutics. Crit Rev Oncol Hematol 98:12–23. https://doi.org/10.1016/j.critrevonc.2015.10.003
Panda AC (2018) Circular RNAs act as miRNA sponges. Adv Exp Med Biol 1087:67–79. https://doi.org/10.1007/978-981-13-1426-1_6
Patop IL, Kadener S (2018) circRNAs in Cancer. Curr Opin Genet Dev 48:121–127. https://doi.org/10.1016/j.gde.2017.11.007
Qi X, Zhang DH, Wu N, Xiao JH, Wang X, Ma W (2015) ceRNA in cancer: possible functions and clinical implications. J Med Genet 52:710–718. https://doi.org/10.1136/jmedgenet-2015-103334
Qu Y, Dou P, Hu M, Xu J, Xia W, Sun H (2019) circRNA–CER mediates malignant progression of breast cancer through targeting the miR–136/MMP13 axis. Mol Med Rep 19:3314–3320. https://doi.org/10.3892/mmr.2019.9965
Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34. https://doi.org/10.3322/caac.21551
Soheilifar MH, Masoudi-Khoram N, Madadi S, Nobari S, Maadi H, Keshmiri Neghab H, Amini R, Pishnamazi M (2022) Angioregulatory microRNAs in breast cancer: molecular mechanistic basis and implications for therapeutic strategies. J Adv Res 37:235–253. https://doi.org/10.1016/j.jare.2021.06.019
Sun D, Zhu D (2020) Circular RNA hsa_circ_0001649 suppresses the growth of osteosarcoma cells via sponging multiple miRNAs. Cell Cycle 19:2631–2643. https://doi.org/10.1080/15384101.2020.1814026
Vasudevan S (2012) Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA 3:311–330. https://doi.org/10.1002/wrna.121
Wang S, Zhang Y, Cai Q, Ma M, Jin LY, Weng M, Zhou D, Tang Z, Wang JD, Quan Z (2019) Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression. Mol Cancer 18:145. https://doi.org/10.1186/s12943-019-1078-z
Wang Y, Chen J, Wang X, Wang K (2020) Mir-140-3p inhibits bladder cancer cell proliferation and invasion by targeting FOXQ1. Aging 12:20366–20379. https://doi.org/10.18632/aging.103828
Xu Y, Yao Y, Leng K, Ji D, Qu L, Liu Y, Cui Y (2018) Increased expression of circular RNA circ_0005230 indicates dismal prognosis in breast cancer and regulates cell proliferation and Invasion via miR-618/ CBX8 signal pathway. Cell Physiol Biochem 51:1710–1722. https://doi.org/10.1159/000495675
Yu J, Zhang H, Zhao C, Li G, Zhang Y, Sun Y (2022) CircRNA circ_0008037 facilitates tumor growth and the Warburg effect via upregulating NUCKS1 by binding to mir-433-3p in non-small cell lung cancer. Thorac Cancer 13:162–172. https://doi.org/10.1111/1759-7714.14235
Zang H, Li Y, Zhang X, Huang G (2020) Circ_0000517 contributes to hepatocellular carcinoma progression by upregulating TXNDC5 via sponging miR-1296-5p. Cancer Manag Res 12:3457–3468. https://doi.org/10.2147/CMAR.S244024
Zeng K, He B, Yang BB, Xu T, Chen X, Xu M, Liu X, Sun H, Pan Y, Wang S (2018) The pro-metastasis effect of circANKS1B in breast cancer. Mol Cancer 17:160. https://doi.org/10.1186/s12943-018-0914-x
Zhang L, Ding F (2019) Hsa_circ_0008945 promoted breast cancer progression by targeting miR-338-3p. Onco Targets Ther 12:6577–6589. https://doi.org/10.2147/OTT.S213994
Zhang HD, Jiang LH, Sun DW, Hou JC, Ji ZL (2018a) CircRNA: a novel type of biomarker for cancer. Breast Cancer 25:1–7. http://doi.org/10.1007/s12282-017-0793-9
Zhang HQ, Zhao G, Ke B, Ma G, Liu GL, Liang H, Liu LR, Hao XS (2018b) Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients. Eur Rev Med Pharmacol Sci 22:1665–1671. http://doi.org/10.26355/eurrev_2018b03_14578
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. https://doi.org/10.1016/j.cca.2021.09.013
Acknowledgements
None.
Funding
None.
Author information
Authors and Affiliations
Contributions
LH: conceived and designed the study, and drafted the first draft of the manuscript. All experiments were completed by all authors. GZ, LH, XB, ZX, FW, GH: analyzed and collated the results. All authors reviewed and critiqued the manuscript, and agreed to the final submission of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethical Approval
Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical Univsersity.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
10528_2023_10407_MOESM1_ESM.tif
Supplementary material 1 (TIF 408.8 kb) Circ_0059457 knockdown inhibited ECAR level in BC cells. MB231 and BT549 cells were transfected with sh-circ_0059457 or sh-NC. The ECAR level was detected by ECAR Kit in MB231 cells (A) and BT549 cells (B).
10528_2023_10407_MOESM2_ESM.tif
Supplementary material 2 (TIF 255.5 kb) Circ_0059457 knockdown reduced EMT in BC cells. MB231 and BT549 cells were transfected with sh-circ_0059457 or sh-NC. The levels of E-cadherin and N-cadherin were detected by WB analysis in MB231 cells (A) and BT549 cells (B). *P < 0.05.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Huang, L., Zhang, G., Han, L. et al. Circ_0059457 Promotes Proliferation, Metastasis, Sphere Formation and Glycolysis in Breast Cancer Cells by Sponging miR-140-3p to Regulate UBE2C. Biochem Genet 62, 125–143 (2024). https://doi.org/10.1007/s10528-023-10407-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-023-10407-8