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Cancer Cell International
Published in: Cancer Cell International 1/2024

Open Access 01-12-2024 | Ovarian Cancer | Research

CircRAD23B promotes proliferation and carboplatin resistance in ovarian cancer cell lines and organoids

Authors: Hui Wang, Yashuang Zhang, Huixian Miao, Ting Xu, Xianglin Nie, Wenjun Cheng

Published in: Cancer Cell International | Issue 1/2024

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Abstract

Background

Circular RNAs (circRNAs) are involved in the regulation of progression and drug resistance in ovarian cancer (OC). In the present study, we aimed to explore the role of circRAD23B, a newly identified circRNA, in the regulation of carboplatin-resistant OC.

Methods

CircRAD23B expression levels were measured using qRT-PCR. The biological roles of circRAD23B were analysed using CCK-8, colony formation, EDU, flow cytometry, and cell viability assays. RNA pull-down and luciferase assays were used to investigate the interactions of circRAD23B with mRNAs and miRNAs.

Results

CircRAD23B was significantly increased in carboplatin-resistant OC tissues. CircRAD23B promoted proliferation and reduced sensitivity to carboplatin in cell lines and patient-derived organoids (PDOs), consistent with in vivo findings. Mechanistically, circRAD23B acted as a molecular sponge, abrogating its inhibitory effect on Y-box binding protein 1 (YBX1) by adsorbing miR-1287-5p. Rescue experiments confirmed that the pro-proliferation and carboplatin resistance mediated by circRAD23B was partially reversed by the upregulation of miR-1287-5p.

Conclusions

Our results demonstrated, for the first time, the role of the circRAD23B/miR-1287-5p/YBX1 axis in OC progression and carboplatin resistance in cell lines, PDOs, and animal models, providing a basis for the development of targeted therapies for patients with OC.
Appendix
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Literature
1.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.CrossRefPubMed
2.
Odunsi K. Immunotherapy in ovarian cancer. ANN ONCOL. 2017;28(suppl8):i1–i7.CrossRef
3.
4.
You Q, Shi HY, Gong CF, Tian XY, Li S. Long non-coding RNA DLX6-AS1 acts as an oncogene by targeting miR-613 in ovarian cancer. Eur Rev Med Pharmacol Sci. 2020;24(16):8243.PubMed
5.
Yang M, Zhai Z, Guo S, Li X, Zhu Y, Wang Y. Long non-coding RNA FLJ33360 participates in ovarian cancer progression by sponging miR-30b-3p. Onco Targets Ther. 2019;12:4469–80.CrossRefPubMedPubMedCentral
6.
Chen Y, Cui Z, Wu Q, Wang H, Xia H, Sun Y. Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer. Bioengineered. 2022;13(5):13893–905.CrossRefPubMedPubMedCentral
7.
Wu M, Qiu Q, Zhou Q, Li J, Yang J, Zheng C, Luo A, Li X, Zhang H, Cheng X, et al. circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the wnt signaling pathway in ovarian cancer. MOL CANCER. 2022;21(1):137.CrossRefPubMedPubMedCentral
8.
Gan X, Zhu H, Jiang X, Obiegbusi SC, Yong M, Long X, Hu J. CircMUC16 promotes autophagy of epithelial ovarian cancer via interaction with ATG13 and miR-199a. MOL CANCER. 2020;19(1):45.CrossRefPubMedPubMedCentral
9.
10.
Chen L, Shan G. CircRNA in cancer: fundamental mechanism and clinical potential. CANCER LETT. 2021;505:49–57.CrossRefPubMed
11.
Ghafouri-Fard S, Najafi S, Hussen BM, Basiri A, Hidayat HJ, Taheri M, Rashnoo F. The role of circular RNAs in the carcinogenesis of bladder Cancer. FRONT ONCOL. 2022;12:801842.CrossRefPubMedPubMedCentral
12.
Shi X, Yang J, Liu M, Zhang Y, Zhou Z, Luo W, Fung KM, Xu C, Bronze MS, Houchen CW et al. Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-beta Signaling Axis in Pancreatic Cancer. GASTROENTEROLOGY 2022, 162(7):2004–2017.
13.
Gu Y, Wang Y, He L, Zhang J, Zhu X, Liu N, Wang J, Lu T, He L, Tian Y, et al. Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via hedgehog signaling. MOL CANCER. 2021;20(1):132.CrossRefPubMedPubMedCentral
14.
Liu Z, Gu S, Wu K, Li L, Dong C, Wang W, Zhou Y. CircRNA-DOPEY2 enhances the chemosensitivity of esophageal cancer cells by inhibiting CPEB4-mediated Mcl-1 translation. J Exp Clin Cancer Res. 2021;40(1):361.CrossRefPubMedPubMedCentral
15.
Rossi F, Beltran M, Damizia M, Grelloni C, Colantoni A, Setti A, Di Timoteo G, Dattilo D, Centron-Broco A, Nicoletti C, et al. Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity. MOL CELL. 2022;82(1):75–89.CrossRefPubMedPubMedCentral
16.
17.
Najafi S. Circular RNAs as emerging players in cervical cancer tumorigenesis; a review to roles and biomarker potentials. INT J BIOL MACROMOL. 2022;206:939–53.CrossRefPubMed
18.
Hua Q, Liu Y, Li M, Li X, Chen W, Diao Q, Ling Y, Jiang Y. Upregulation of Circ_0035266 contributes to the malignant progression of inflammation-Associated Malignant transformed cells Induced by Tobacco-Specific Carcinogen NNK. TOXICOL SCI. 2022;189(2):203–15.CrossRefPubMed
19.
Zhang M, Xu Y, Zhang Y, Li B, Lou G. Circular RNA circE2F2 promotes malignant progression of ovarian cancer cells by upregulating the expression of E2F2 protein via binding to HuR protein. CELL SIGNAL. 2021;84:110014.CrossRefPubMed
20.
Wang S, Li Z, Zhu G, Hong L, Hu C, Wang K, Cui K, Hao C. RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis. J OVARIAN RES. 2021;14(1):154.CrossRefPubMedPubMedCentral
21.
Wang H, Zhang X, Qiao L, Wang H. CircRNA circ_0000554 promotes ovarian cancer invasion and proliferation by regulating miR-567. Environ Sci Pollut Res Int. 2022;29(13):19072–80.CrossRefPubMed
22.
Li H, Luo F, Jiang X, Zhang W, Xiang T, Pan Q, Cai L, Zhao J, Weng D, Li Y et al. CircITGB6 promotes ovarian cancer cisplatin resistance by resetting tumor-associated macrophage polarization toward the M2 phenotype. J IMMUNOTHER CANCER 2022, 10(3).
23.
Ge L, Sun Y, Shi Y, Liu G, Teng F, Geng Z, Chen X, Xu H, Xu J, Jia X. Plasma circRNA microarray profiling identifies novel circRNA biomarkers for the diagnosis of ovarian cancer. J OVARIAN RES. 2022;15(1):58.CrossRefPubMedPubMedCentral
24.
25.
Li J, Tian L, Jing Z, Guo Z, Nan P, Liu F, Zou S, Yang L, Xie X, Zhu Y, et al. Cytoplasmic RAD23B interacts with CORO1C to synergistically promote colorectal cancer progression and metastasis. CANCER LETT. 2021;516:13–27.CrossRefPubMed
26.
Wang J, Liu R, Mo H, Xiao X, Xu Q, Zhao W. Deubiquitinase PSMD7 promotes the proliferation, invasion, and cisplatin resistance of gastric cancer cells by stabilizing RAD23B. INT J BIOL SCI. 2021;17(13):3331–42.CrossRefPubMedPubMedCentral
27.
Linge A, Maurya P, Friedrich K, Baretton GB, Kelly S, Henry M, Clynes M, Larkin A, Meleady P. Identification and functional validation of RAD23B as a potential protein in human breast cancer progression. J PROTEOME RES. 2014;13(7):3212–22.CrossRefPubMed
28.
Han W, Wang L, Zhang L, Wang Y, Li Y. Circular RNA circ-RAD23B promotes cell growth and invasion by miR-593-3p/CCND2 and miR-653-5p/TIAM1 pathways in non-small cell lung cancer. Biochem Biophys Res Commun. 2019;510(3):462–6.CrossRefPubMed
29.
Lan X, Liu X, Sun J, Yuan Q, Li J. CircRAD23B facilitates proliferation and invasion of esophageal cancer cells by sponging miR-5095. Biochem Biophys Res Commun. 2019;516(2):357–64.CrossRefPubMed
30.
Han B, Wang X, Yin X. Knockdown of circRAD23B exerts Antitumor Response in Colorectal Cancer via the regulation of miR-1205/TRIM44 axis. Dig Dis Sci. 2022;67(2):504–15.CrossRefPubMed
31.
Kopper O, de Witte CJ, Lohmussaar K, Valle-Inclan JE, Hami N, Kester L, Balgobind AV, Korving J, Proost N, Begthel H, et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. NAT MED. 2019;25(5):838–49.CrossRefPubMed
32.
Chen X, Han P, Zhou T, Guo X, Song X, Li Y. circRNADb: a comprehensive database for human circular RNAs with protein-coding annotations. Sci Rep. 2016;6:34985.CrossRefPubMedPubMedCentral
33.
Dudekula DB, Panda AC, Grammatikakis I, De S, Abdelmohsen K, Gorospe M. CircInteractome: a web tool for exploring circular RNAs and their interacting proteins and microRNAs. RNA BIOL. 2016;13(1):34–42.CrossRefPubMed
34.
Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. NUCLEIC ACIDS RES. 2014;42(Database issue):D92–7.CrossRefPubMed
35.
Sun H, Wang H, Wang X, Aoki Y, Wang X, Yang Y, Cheng X, Wang Z, Wang X. Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. THERANOSTICS 2020, 10(15):6928–6945.
36.
Wang X, Chen T, Li C, Li W, Zhou X, Li Y, Luo D, Zhang N, Chen B, Wang L, et al. CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR. J HEMATOL ONCOL. 2022;15(1):122.CrossRefPubMedPubMedCentral
37.
Bai N, Peng E, Qiu X, Lyu N, Zhang Z, Tao Y, Li X, Wang Z. circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346. J Exp Clin Cancer Res. 2018;37(1):172.CrossRefPubMedPubMedCentral
38.
Cheng H, Wang N, Tian J, Li Y, Ren L, Shi Z. Circular RNA Circ_0025033 promotes the evolvement of Ovarian Cancer through the regulation of miR-330-5p/KLK4 Axis. CANCER MANAG RES. 2020;12:2753–65.CrossRefPubMedPubMedCentral
39.
Basaki Y, Hosoi F, Oda Y, Fotovati A, Maruyama Y, Oie S, Ono M, Izumi H, Kohno K, Sakai K, et al. Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. Oncogene. 2007;26(19):2736–46.CrossRefPubMed
40.
Li Y, Zhang L, Zhao Y, Peng H, Zhang N, Bai W. MEG3 sponges miRNA-376a and YBX1 to regulate angiogenesis in ovarian cancer endothelial cells. Heliyon. 2023;9(2):e13204.CrossRefPubMedPubMedCentral
41.
Gao W, Chen L, Lin L, Yang M, Li T, Wei H, Sha C, Xing J, Zhang M, Zhao S et al. SIAH1 reverses chemoresistance in epithelial ovarian cancer via ubiquitination of YBX-1. ONCOGENESIS 2022, 11(1):13.
42.
Mordovkina D, Lyabin DN, Smolin EA, Sogorina EM, Ovchinnikov LP, Eliseeva I. Y-Box binding proteins in mRNP Assembly, translation, and Stability Control. Biomolecules 2020, 10(4).
43.
Fang J, Hong H, Xue X, Zhu X, Jiang L, Qin M, Liang H, Gao L. A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548 g in the cytoplasm and interacting with YBX1 in the nucleus. CANCER LETT. 2019;442:222–32.CrossRefPubMed
44.
Xu J, Ji L, Liang Y, Wan Z, Zheng W, Song X, Gorshkov K, Sun Q, Lin H, Zheng X, et al. CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal Transduct Target Ther. 2020;5(1):298.CrossRefPubMedPubMedCentral
45.
Chen Q, Wang H, Li Z, Li F, Liang L, Zou Y, Shen H, Li J, Xia Y, Cheng Z, et al. Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription. J HEPATOL. 2022;76(1):135–47.CrossRefPubMed
46.
Hong X, Li Q, Li J, Chen K, He Q, Zhao Y, Liang Y, Zhao Y, Qiao H, Liu N, et al. CircIPO7 promotes Nasopharyngeal Carcinoma Metastasis and Cisplatin Chemoresistance by facilitating YBX1 Nuclear localization. CLIN CANCER RES. 2022;28(20):4521–35.CrossRefPubMed
Metadata
Title
CircRAD23B promotes proliferation and carboplatin resistance in ovarian cancer cell lines and organoids
Authors
Hui Wang
Yashuang Zhang
Huixian Miao
Ting Xu
Xianglin Nie
Wenjun Cheng
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-024-03228-1

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