Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Analysis of Potential Circular RNAs in Regulating Imatinib Resistance of Gastrointestinal Stromal Tumor

Author(s): Jingyi Yan*, Xiaolei Chen, Qiantong Dong, Ji Lin and Xuecheng Sun*

Volume 27, Issue 9, 2024

Published on: 27 September, 2023

Page: [1371 - 1380] Pages: 10

DOI: 10.2174/1386207326666230822100024

Price: $65

Abstract

Introduction: Recent studies have found that circular RNA is an abundant RNA species that belongs to part of the competing endogenous RNA network (ceRNA), which was proven to play an important role in the development, diagnosis and progress of diseases. However, the function of circRNAs in imatinib resistance in Gastrointestinal stromal tumor (GIST) are poorly understood so for. The present study aimed to screen and predict the potential circRNAs in imatinib resistance of GIST using microarray analysis.

Methods: We determined the expression of circular RNAs in paired normal gastric tissues (N), primary GIST (gastrointestinal stromal tumor) tissues (YC) and imatinib mesylate secondary resistance GIST tissues (C) with microarray and predicted 8677 dysregulated circular RNAs.

Results: Compared with the YC group, we identified 15 circRNAs that were up-regulated and 8 circRNAs that were down-regulated in the C group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these host linear transcripts that differentially express circular RNAs are involved in many key biological pathways, predicting the potential tumor-genesis and drug resistance mechanismrelated to HIF-1 pathway, later we draw the cirRNA-miRNA-mRNA network involved in the HIF-1 pathway and found several dysregulated circRNAs and the relationship between circRNA-miRNAs-mRNA, such as circRNA_06551, circRNA_14668, circRNA_04497, circRNA_08683, circRNA_09923(Green, down-regulation) and circRNA_23636, circRNA_15734 (Red, up-regulation).

Conclusion: Taken together, we identified a panel of dysregulated circRNAs that may be potential biomarkers even therapy relevant to the GIST, especially imatinib secondary resistance GIST.

Graphical Abstract

[1]
Kelly, C.M.; Gutierrez Sainz, L.; Chi, P. The management of metastatic GIST: Current standard and investigational therapeutics. J. Hematol. Oncol., 2021, 14(1), 2.
[http://dx.doi.org/10.1186/s13045-020-01026-6] [PMID: 33402214]
[2]
Jia, N.; Tong, H.; Zhang, Y.; Katayama, H.; Wang, Y.; Lu, W.; Zhang, S.; Wang, J. CeRNA expression profiling identifies KIT-related circRNA-miRNA-mRNA networks in gastrointestinal stromal tumour. Front. Genet., 2019, 10, 825.
[http://dx.doi.org/10.3389/fgene.2019.00825] [PMID: 31552107]
[3]
Heinrich, M.C.; Jones, R.L.; von Mehren, M.; Schöffski, P.; Serrano, C.; Kang, Y.K.; Cassier, P.A.; Mir, O.; Eskens, F.; Tap, W.D.; Rutkowski, P.; Chawla, S.P.; Trent, J.; Tugnait, M.; Evans, E.K.; Lauz, T.; Zhou, T.; Roche, M.; Wolf, B.B.; Bauer, S.; George, S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): A multicentre, open-label, phase 1 trial. Lancet Oncol., 2020, 21(7), 935-946.
[http://dx.doi.org/10.1016/S1470-2045(20)30269-2] [PMID: 32615108]
[4]
Joensuu, H.; Hohenberger, P.; Corless, C.L. Gastrointestinal stromal tumour. Lancet, 2013, 382(9896), 973-983.
[http://dx.doi.org/10.1016/S0140-6736(13)60106-3] [PMID: 23623056]
[5]
Mohammadi, M.; Gelderblom, H. Systemic therapy of advanced/metastatic gastrointestinal stromal tumors: An update on progress beyond imatinib, sunitinib, and regorafenib. Expert Opin. Investig. Drugs, 2021, 30(2), 143-152.
[http://dx.doi.org/10.1080/13543784.2021.1857363] [PMID: 33252274]
[6]
Li, J.; Sun, D.; Pu, W.; Wang, J.; Peng, Y. Circular RNAs in cancer: Biogenesis, function, and clinical significance. Trends Cancer, 2020, 6(4), 319-336.
[http://dx.doi.org/10.1016/j.trecan.2020.01.012] [PMID: 32209446]
[7]
Bai, S.; Wu, Y.; Yan, Y.; Shao, S.; Zhang, J.; Liu, J.; Hui, B.; Liu, R.; Ma, H.; Zhang, X.; Ren, J. Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell renal cell carcinoma. Sci. Rep., 2020, 10(1), 13659.
[http://dx.doi.org/10.1038/s41598-020-70484-2] [PMID: 32788609]
[8]
Zhao, M.; Ma, W.; Ma, C. Circ_0067934 promotes non-small cell lung cancer development by regulating miR-1182/KLF8 axis and activating Wnt/β-catenin pathway. Biomed. Pharmacother., 2020, 129, 110461.
[http://dx.doi.org/10.1016/j.biopha.2020.110461] [PMID: 32768951]
[9]
Geng, Y.; Bao, Y.; Deng, L.; Su, D.; Zheng, H.; Zhang, W. Circular RNA hsa_circ_0014130 inhibits apoptosis in non–small cell lung cancer by sponging miR-136-5p and upregulating BCL2. Mol. Cancer Res., 2020, 18(5), 748-756.
[http://dx.doi.org/10.1158/1541-7786.MCR-19-0998] [PMID: 32060230]
[10]
Zhou, Y.; Zheng, X.; Xu, B.; Chen, L.; Wang, Q.; Deng, H.; Jiang, J. Circular RNA hsa_circ_0004015 regulates the proliferation, invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway. Biochem. Biophys. Res. Commun., 2019, 508(2), 527-535.
[http://dx.doi.org/10.1016/j.bbrc.2018.11.157] [PMID: 30509491]
[11]
Bolger, A.M.; Lohse, M.; Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 2014, 30(15), 2114-2120.
[http://dx.doi.org/10.1093/bioinformatics/btu170] [PMID: 24695404]
[12]
Li, H.; Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics, 2010, 26(5), 589-595.
[http://dx.doi.org/10.1093/bioinformatics/btp698] [PMID: 20080505]
[13]
Gao, Y.; Wang, J.; Zhao, F. CIRI: An efficient and unbiased algorithm for de novo circular RNA identification. Genome Biol., 2015, 16(1), 4.
[http://dx.doi.org/10.1186/s13059-014-0571-3] [PMID: 25583365]
[14]
Anders, S.; McCarthy, D.J.; Chen, Y.; Okoniewski, M.; Smyth, G.K.; Huber, W.; Robinson, M.D. Count-based differential expression analysis of RNA sequencing data using R and Bioconductor. Nat. Protoc., 2013, 8(9), 1765-1786.
[http://dx.doi.org/10.1038/nprot.2013.099] [PMID: 23975260]
[15]
Enright, A.J.; John, B.; Gaul, U.; Tuschl, T.; Sander, C.; Marks, D.S. MicroRNA targets in drosophila. Genome Biol., 2003, 5(1), R1.
[http://dx.doi.org/10.1186/gb-2003-5-1-r1] [PMID: 14709173]
[16]
Yan, J.; Chen, D.; Chen, X.; Sun, X.; Dong, Q.; Du, Z.; Wang, T. Identification of imatinib-resistant long non-coding RNAs in gastrointestinal stromal tumors. Oncol. Lett., 2019, 17(2), 2283-2295.
[PMID: 30675294]
[17]
Dennis, G., Jr; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol., 2003, 4(5), P3.
[http://dx.doi.org/10.1186/gb-2003-4-5-p3] [PMID: 12734009]
[18]
The Gene Ontology Consortium. The gene ontology resource: 20 years and still going strong. Nucleic Acids Res., 2019, 47(D1), D330-D338.
[http://dx.doi.org/10.1093/nar/gky1055] [PMID: 30395331]
[19]
Wen, C.; Xu, G.; He, S.; Huang, Y.; Shi, J.; Wu, L.; Zhou, H. Screening circular RNAs related to acquired gefitinib resistance in non-small cell lung cancer cell lines. J. Cancer, 2020, 11(13), 3816-3826.
[http://dx.doi.org/10.7150/jca.39783] [PMID: 32328186]
[20]
Zhou, W.Y.; Cai, Z.R.; Liu, J.; Wang, D.S.; Ju, H.Q.; Xu, R.H. Circular RNA: Metabolism, functions and interactions with proteins. Mol. Cancer, 2020, 19(1), 172.
[http://dx.doi.org/10.1186/s12943-020-01286-3] [PMID: 33317550]
[21]
Huang, A.; Zheng, H.; Wu, Z.; Chen, M.; Huang, Y. Circular RNA-protein interactions: Functions, mechanisms, and identification. Theranostics, 2020, 10(8), 3503-3517.
[http://dx.doi.org/10.7150/thno.42174] [PMID: 32206104]
[22]
Kristensen, L.S.; Andersen, M.S.; Stagsted, L.V.W.; Ebbesen, K.K.; Hansen, T.B.; Kjems, J. The biogenesis, biology and characterization of circular RNAs. Nat. Rev. Genet., 2019, 20(11), 675-691.
[http://dx.doi.org/10.1038/s41576-019-0158-7] [PMID: 31395983]
[23]
Zhao, Y.; Zheng, R.; Chen, J.; Ning, D. CircRNA CDR1as/miR-641/HOXA9 pathway regulated stemness contributes to cisplatin resistance in non-small cell lung cancer (NSCLC). Cancer Cell Int., 2020, 20(1), 289.
[http://dx.doi.org/10.1186/s12935-020-01390-w] [PMID: 32655321]
[24]
Xu, T.; Wang, M.; Jiang, L.; Ma, L.; Wan, L.; Chen, Q.; Wei, C.; Wang, Z. CircRNAs in anticancer drug resistance: Recent advances and future potential. Mol. Cancer, 2020, 19(1), 127.
[http://dx.doi.org/10.1186/s12943-020-01240-3] [PMID: 32799866]
[25]
Hong, W.; Xue, M.; Jiang, J.; Zhang, Y.; Gao, X. Circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC). J. Exp. Clin. Cancer Res., 2020, 39(1), 149.
[http://dx.doi.org/10.1186/s13046-020-01648-1] [PMID: 32746878]
[26]
Si, W.; Li, Y.; Ye, S.; Li, Z.; Liu, Y.; Kuang, W.; Chen, D.; Zhu, M. Methyltransferase 3 mediated miRNA m6A methylation promotes stress granule formation in the early stage of acute ischemic stroke. Front. Mol. Neurosci., 2020, 13, 103.
[http://dx.doi.org/10.3389/fnmol.2020.00103] [PMID: 32581712]
[27]
Hua, X.; Sun, Y.; Chen, J.; Wu, Y.; Sha, J.; Han, S.; Zhu, X. Circular RNAs in drug resistant tumors. Biomed. Pharmacother., 2019, 118, 109233.
[http://dx.doi.org/10.1016/j.biopha.2019.109233] [PMID: 31351436]
[28]
Sang, Y.; Chen, B.; Song, X.; Li, Y.; Liang, Y.; Han, D.; Zhang, N.; Zhang, H.; Liu, Y.; Chen, T.; Li, C.; Wang, L.; Zhao, W.; Yang, Q. circRNA_0025202 regulates tamoxifen sensitivity and tumor progression via regulating the miR-182-5p/FOXO3a axis in breast cancer. Mol. Ther., 2019, 27(9), 1638-1652.
[http://dx.doi.org/10.1016/j.ymthe.2019.05.011] [PMID: 31153828]
[29]
Huang, X.; Li, Z.; Zhang, Q.; Wang, W.; Li, B.; Wang, L.; Xu, Z.; Zeng, A.; Zhang, X.; Zhang, X.; He, Z.; Li, Q.; Sun, G.; Wang, S.; Li, Q.; Wang, L.; Zhang, L.; Xu, H.; Xu, Z. Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression. Mol. Cancer, 2019, 18(1), 71.
[http://dx.doi.org/10.1186/s12943-019-0969-3] [PMID: 30927924]
[30]
Sun, G.; Li, Z.; He, Z.; Wang, W.; Wang, S.; Zhang, X.; Cao, J.; Xu, P.; Wang, H.; Huang, X.; Xia, Y.; Lv, J.; Xuan, Z.; Jiang, T.; Fang, L.; Yang, J.; Zhang, D.; Xu, H.; Xu, Z. Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression. J. Exp. Clin. Cancer Res., 2020, 39(1), 246.
[http://dx.doi.org/10.1186/s13046-020-01758-w] [PMID: 33198772]
[31]
Zhang, S.; Cheng, J.; Quan, C.; Wen, H.; Feng, Z.; Hu, Q.; Zhu, J.; Huang, Y.; Wu, X. circCELSR1 (hsa_circ_0063809) contributes to paclitaxel resistance of ovarian cancer cells by regulating FOXR2 expression via miR-1252. Mol. Ther. Nucleic Acids, 2020, 19, 718-730.
[http://dx.doi.org/10.1016/j.omtn.2019.12.005] [PMID: 31945729]
[32]
Zheng, Q.; Bao, C.; Guo, W.; Li, S.; Chen, J.; Chen, B.; Luo, Y.; Lyu, D.; Li, Y.; Shi, G.; Liang, L.; Gu, J.; He, X.; Huang, S. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat. Commun., 2016, 7(1), 11215.
[http://dx.doi.org/10.1038/ncomms11215] [PMID: 27050392]
[33]
Li, Z.; Huang, C.; Bao, C.; Chen, L.; Lin, M.; Wang, X.; Zhong, G.; Yu, B.; Hu, W.; Dai, L.; Zhu, P.; Chang, Z.; Wu, Q.; Zhao, Y.; Jia, Y.; Xu, P.; Liu, H.; Shan, G. Exon-intron circular RNAs regulate transcription in the nucleus. Nat. Struct. Mol. Biol., 2015, 22(3), 256-264.
[http://dx.doi.org/10.1038/nsmb.2959] [PMID: 25664725]
[34]
Zhang, Y.; Zhang, X.O.; Chen, T.; Xiang, J.F.; Yin, Q.F.; Xing, Y.H.; Zhu, S.; Yang, L.; Chen, L.L. Circular intronic long noncoding RNAs. Mol. Cell, 2013, 51(6), 792-806.
[http://dx.doi.org/10.1016/j.molcel.2013.08.017] [PMID: 24035497]
[35]
Balamurugan, K. HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int. J. Cancer, 2016, 138(5), 1058-1066.
[http://dx.doi.org/10.1002/ijc.29519] [PMID: 25784597]
[36]
Albadari, N.; Deng, S.; Li, W. The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy. Expert Opin. Drug Discov., 2019, 14(7), 667-682.
[http://dx.doi.org/10.1080/17460441.2019.1613370] [PMID: 31070059]
[37]
Wigerup, C.; Påhlman, S.; Bexell, D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol. Ther., 2016, 164, 152-169.
[http://dx.doi.org/10.1016/j.pharmthera.2016.04.009] [PMID: 27139518]
[38]
Xu, K.; Zhan, Y.; Yuan, Z.; Qiu, Y.; Wang, H.; Fan, G.; Wang, J.; Li, W.; Cao, Y.; Shen, X.; Zhang, J.; Liang, X.; Yin, P. Hypoxia induces drug resistance in colorectal cancer through the HIF-1α/miR-338-5p/IL-6 feedback loop. Mol. Ther., 2019, 27(10), 1810-1824.
[http://dx.doi.org/10.1016/j.ymthe.2019.05.017] [PMID: 31208913]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy