Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is a serious malignant cancer. The treatment effect of ESCC is relatively poor and needs further improvement. According to reports, circular RNAs (circRNAs) actively participate in human carcinogenesis. More explorations are needed about the action of circRNAs in ESCC.
Methods
Circ_0024108, miR-488-3p, and USP14 was quantified by a qRT-PCR or immunoblotting method. Cell proliferation evaluation was performed by MTT, EdU, and colony formation assays. Evaluation of cell motility and invasiveness was conducted using wound healing assay and transwell assay. The regulatory mechanism of circ_0024108, miR-488-3p, and USP14 was detected by RNA pull-down assay and dual-luciferase reporter assay.
Results
Circ_0024108 and USP14 were significantly overexpressed in ESCC, while miR-488-3p was underexpressed. Deficiency of circ_0024108 impeded cell growth, motility, and invasiveness. Circ_0024108 regulated the expression of USP14 in ESCC cells via miR-488-3p. Also, circ_0024108 was present at high levels in serum exosomes from ESCC patients with high specificity and sensitivity.
Conclusions
Taken together, circ_0024108 participated in the progress of ESCC through the miR-488-3p/USP14 axis. Circ_0024108 was differentially expressed in serum exosomes. Circ_0024108 might be a potential biomarker for the diagnosis of ESCC.
Similar content being viewed by others
Data availability
All data generated or analysed during this study are included in this published article (and its supplementary information files).
References
Allum WH, Bonavina L, Cassivi SD, Cuesta MA, Dong ZM, Felix VN, Figueredo E, Gatenby PA, Haverkamp L, Ibraev MA, Krasna MJ, Lambert R, Langer R, Lewis MP, Nason KS, Parry K, Preston SR, Ruurda JP, Schaheen LW, Tatum RP, Turkin IN, van der Horst S, van der Peet DL, van der Sluis PC, van Hillegersberg R, Wormald JC, Wu PC, Zonderhuis BM. Surgical treatments for esophageal cancers. Ann N Y Acad Sci. 2014;1325:242–68.
An T, Qin S, Xu Y, Tang Y, Huang Y, Situ B, Inal JM, Zheng L. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles. 2015;4:27522.
Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut. 2015;64:381–7.
Chen X, Jiang J, Zhao Y, Wang X, Zhang C, Zhuan L, Zhang D, Zheng Y. Circular RNA circNTRK2 facilitates the progression of esophageal squamous cell carcinoma through up-regulating NRIP1 expression via miR-140-3p. J Exp Clin Cancer Res. 2020;39:133.
Gao DC, Hou B, Zhou D, Liu QX, Zhang K, Lu X, Zhang J, Zheng H, Dai JG. Tumor-derived exosomal miR-103a-2-5p facilitates esophageal squamous cell carcinoma cell proliferation and migration. Eur Rev Med Pharmacol Sci. 2020;24:6097–110.
Gao L, Wang L, Dai T, Jin K, Zhang Z, Wang S, Xie F, Fang P, Yang B, Huang H, van Dam H, Zhou F, Zhang L. Tumor-derived exosomes antagonize innate antiviral immunity. Nat Immunol. 2018;19:233–45.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.
Hu X, Wu D, He X, Zhao H, He Z, Lin J, Wang K, Wang W, Pan Z, Lin H, Wang M. circGSK3beta promotes metastasis in esophageal squamous cell carcinoma by augmenting beta-catenin signaling. Mol Cancer. 2019;18:160.
Jena BC, Mandal M. The emerging roles of exosomes in anti-cancer drug resistance and tumor progression: An insight towards tumor-microenvironment interaction. Biochim Biophys Acta Rev Cancer. 2021;1875:188488.
Jiang C, Xu D, You Z, Xu K, Tian W. Dysregulated circRNAs and ceRNA network in esophageal squamous cell carcinoma. Front Biosci (Landmark Ed). 2019;24:277–90.
Kang M, Ren M, Li Y, Fu Y, Deng M, Li C. Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA. J Exp Clin Cancer Res. 2018;37:171.
Kok VC, Yu CC. Cancer-derived exosomes: their role in cancer biology and biomarker development. Int J Nanomedicine. 2020;15:8019–36.
Li J, Sun D, Pu W, Wang J, Peng Y. Circular RNAs in cancer: biogenesis, function, and clinical significance. Trends Cancer. 2020;6:319–36.
Li X, Yang L, Chen LL. The biogenesis, functions, and challenges of circular RNAs. Mol Cell. 2018;71:428–42.
Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, Chen D, Gu J, He X, Huang S. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015;25:981–4.
Liu J, Liu T, Wang X, He A. Circles reshaping the RNA world: from waste to treasure. Mol Cancer. 2017;16:58.
Liu J, Ren L, Li S, Li W, Zheng X, Yang Y, Fu W, Yi J, Wang J, Du G. The biology, function, and applications of exosomes in cancer. Acta Pharm Sin B. 2021;11:2783–97.
Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, Wu M. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16:94.
Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149:1700–15.
Qu S, Liu Z, Yang X, Zhou J, Yu H, Zhang R, Li H. The emerging functions and roles of circular RNAs in cancer. Cancer Lett. 2018;414:301–9.
Qu S, Zhong Y, Shang R, Zhang X, Song W, Kjems J, Li H. The emerging landscape of circular RNA in life processes. RNA Biol. 2017;14:992–9.
Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR. Targeting Tumor Microenvironment for Cancer Therapy. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20040840.
Sha B, Chen X, Wu H, Li M, Shi J, Wang L, Liu X, Chen P, Hu T, Li P. Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma. Apoptosis. 2019;24:826–36.
Shang A, Gu C, Wang W, Wang X, Sun J, Zeng B, Chen C, Chang W, Ping Y, Ji P, Wu J, Quan W, Yao Y, Zhou Y, Sun Z, Li D. Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-beta1 axis. Mol Cancer. 2020;19:117.
van Rossum PSN, Mohammad NH, Vleggaar FP, van Hillegersberg R. Treatment for unresectable or metastatic oesophageal cancer: current evidence and trends. Nat Rev Gastroenterol Hepatol. 2018;15:235–49.
Wang Q, Yang L, Fan Y, Tang W, Sun H, Xu Z, Zhou J, Zhang Y, Zhu B, Cao X. Circ-ZDHHC5 accelerates esophageal squamous cell carcinoma progression in vitro via miR-217/ZEB1 axis. Front Cell Dev Biol. 2020;8:570305.
Yang E, Wang X, Gong Z, Yu M, Wu H, Zhang D. Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression. Signal Transduct Target Ther. 2020;5:242.
Yang Y, Li H, He Z, Xie D, Ni J, Lin X. MicroRNA-488-3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma. J Cell Biochem. 2019;120:18702–13.
Yin K, Liu X. CircMMP1 promotes the progression of glioma through miR-433/HMGB3 axis in vitro and in vivo. IUBMB Life. 2020;72:2508–24.
Zang R, Qiu X, Song Y, Wang Y. Exosomes mediated transfer of circ_0000337 Contributes to cisplatin (CDDP) resistance of esophageal cancer by regulating JAK2 via miR-377-3p. Front Cell Dev Biol. 2021;9:673237.
Zhang B, Li M, Huang P, Guan XY, Zhu YH. Overexpression of ubiquitin specific peptidase 14 predicts unfavorable prognosis in esophageal squamous cell carcinoma. Thorac Cancer. 2017;8:344–9.
Zhang J, Zhang D, Sun L. Knockdown of ubiquitin-specific protease 14 (USP14) inhibits the proliferation and tumorigenesis in esophageal squamous cell carcinoma cells. Oncol Res. 2017;25:249–57.
Zhang Z, Yang T, Xiao J. Circular RNAs: promising biomarkers for human diseases. EBioMedicine. 2018;34:267–74.
Zhou R, Wu Y, Wang W, Su W, Liu Y, Wang Y, Fan C, Li X, Li G, Li Y, Xiong W, Zeng Z. Circular RNAs (circRNAs) in cancer. Cancer Lett. 2018;425:134–42.
Acknowledgements
Not applicable.
Funding
None.
Author information
Authors and Affiliations
Corresponding author
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.
11748_2023_1909_MOESM1_ESM.tif
Supplementary file1 (TIF 688 KB) Figure S1 Effect of circ_0024108 depletion on PCNA expression in ESCC cells. The protein expression of PCNA was measured by immunoblotting in ECA109 and KYSE410 cells transfected as indicated. The data are presented as the mean ± SD; *P < 0.05.
11748_2023_1909_MOESM2_ESM.tif
Supplementary file2 (TIF 688 KB) Figure S2. Identification and expression detection after exosomes treatment. (A) circ_0024108 expression in si-circ_0024108 and oe-circ_0024108 exosomes of ECA109 cells. (B) miR-488-3p expression in KYSE410 cells after co-culture with si-circ_0024108 and oe-circ_0024108 exosomes detected by qRT-PCR. (C and D) USP14 expression in KYSE410 cells after co-culture with si-circ_0024108 and oe-circ_0024108 exosomes detected by qRT-PCR and immunoblotting. The data are presented as the mean ± SD; qRT-PCR, quantitative real-time polymerase chain reaction; *P < 0.05.
11748_2023_1909_MOESM3_ESM.tif
Supplementary file3 (TIF 371 KB) Figure S3. The regulation of sh-circ_0024108 in the expression of miR-488-3p and USP14 in the xenograft tumors. (A) miR-488-3p expression by qRT-PCR in the xenograft tumors transduced with sh-NC or sh-circ_0024108. (B) USP14 protein level by immunoblotting in the xenograft tumors. The data are presented as the mean ± SD; qRT-PCR, quantitative real-time polymerase chain reaction; *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
Hu, T., Peng, H., Yang, F. et al. Circ_0024108 promotes the progression of esophageal cancer cells. Gen Thorac Cardiovasc Surg 71, 418–431 (2023). https://doi.org/10.1007/s11748-023-01909-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11748-023-01909-8