Review
Open Access
Impact of exosomal and cell-free circRNAs on cancer drug resistance
Heidi Schwarzenbach
Department of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Abstract

Cancer is the most lethal disease in humans. Despite substantial advancements in cancer therapy during the last decades, the effectiveness of chemotherapeutic agents is limited since many patients develop drug resistance. Drug resistance leads to tumor recurrence and remains a major complication in cancer therapy. Modulated levels of circular RNAs (circRNAs) in various tumors are involved in drug resistance, tumor progression and recurrence. CircRNAs have been detected in different body fluids as well as in exosomes. They shuttle through the blood circulation as cell-free molecules or in exosomes, where they are transported to various cells to propagate malignancy. The current review describes the molecular factors that influence the response to targeted therapies, and summarizes the recent findings on the impact of extracellular circRNAs in drug resistance along with their targeted molecular pathways. Additionally, the potential clinical application of circRNAs as therapeutic agents as well as diagnostic and prognostic markers is also discussed.

Keywords

cancer; circRNAs; chemoresistance; plasma; serum; exosomes; therapy

Preview
References
  • [1]Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature 2004, 432(7015):316–323.
  • [2]Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011, 146(6):873–887.
  • [3]Jonckheere S, Adams J, De Groote D, Campbell K, Berx G, et al. Epithelial-Mesenchymal Transition (EMT) as a Therapeutic Target. Cells Tissues Org. 2022, 211(2):157–182.
  • [4]Rodriguez FJ, Lewis-Tuffin LJ, Anastasiadis PZ. E-cadherin’s dark side: Possible role in tumor progression. Biochim. Biophys. Acta, Rev. Cancer 2012, 1826(1):23–31.
  • [5]Géraud C, Koch PS, Damm F, Schledzewski K, Goerdt S. The metastatic cycle: Metastatic niches and cancer cell dissemination. J. Dtsch. Dermatol. 2014, 12(11):1012–1019.
  • [6]Klein CA. Cancer progression and the invisible phase of metastatic colonization. Nat. Rev. Cancer 2020, 20(11):681–694.
  • [7]de Visser KE, Joyce JA. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell 2023, 41(3):374–403.
  • [8]Longley D, Johnston P. Molecular mechanisms of drug resistance. J. Pathol. 2005, 205(2):275–292.
  • [9]Chaplin DD. Overview of the immune response. J. Allergy Clin. Immun. 2010, 125(2):S3–S23.
  • [10]Zhou Y, Tang W, Zhuo H, Zhu D, Rong D, et al. Cancer-associated fibroblast exosomes promote chemoresistance to cisplatin in hepatocellular carcinoma through circZFR targeting signal transducers and activators of transcription (STAT3)/ nuclear factor -kappa B (NF-κB) pathway. Bioengineered 2022, 13(3):4786–4797.
  • [11]Tang S, Ning Q, Yang L, Mo Z, Tang S. Mechanisms of immune escape in the cancer immune cycle. Int. Immunopharmacol. 2020, 86:106700.
  • [12]Esteller M. Epigenetics in Cancer. New Engl. J. Med. 2008, 358(11):1148–1159.
  • [13]Ducasse M, Brown MA. Epigenetic aberrations and cancer. Mol. Cancer 2005, 5:1–10.
  • [14]Schwarzenbach H, Gahan PB. Resistance to cis- And carboplatin initiated by epigenetic changes in ovarian cancer patients. Cancer Drug Resistance 2019, 2(2):271–296.
  • [15]Chen L, Shan G. CircRNA in cancer: Fundamental mechanism and clinical potential. Cancer Lett. 2021, 505:49–57.
  • [16]Khan S, Jha A, Panda AC, Dixit A. Cancer-Associated circRNA–miRNA–mRNA Regulatory Networks: A Meta-Analysis. Front. Mol. Biosci. 2021, 8:671309.
  • [17]Zhang F, Jiang J, Qian H, Yan Y, Xu W. Exosomal circRNA: emerging insights into cancer progression and clinical application potential. J. Hematol. Oncol. 2023, 16(1):67.
  • [18]Park EG, Ha H, Lee DH, Kim WR, Lee YJ, et al. Genomic Analyses of Non-Coding RNAs Overlapping Transposable Elements and Its Implication to Human Diseases. Int. J. Mol. Sci. 2022, 23(16):8950.
  • [19]Zhang W, He Y, Zhang Y. CircRNA in ocular neovascular diseases: Fundamental mechanism and clinical potential. Pharmacol. Res. 2023, 197:106946.
  • [20]Li J, Zhang G, Liu CG, Xiang X, Le MTN, et al. The potential role of exosomal circRNAs in the tumor microenvironment: insights into cancer diagnosis and therapy. Theranostics 2022, 12(1):87–104.
  • [21]Chen J, Gu J, Tang M, Liao Z, Tang R, et al. Regulation of cancer progression by circRNA and functional proteins. J. Cell Physiol. 2022, 237(1):373–388.
  • [22]Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013, 495(7441):384–388.
  • [23]Bartel DP. MicroRNAs: Target Recognition and Regulatory Functions. Cell 2009, 136(2):215–233.
  • [24]Schwarzenbach H. Interplay of microRNAs and circRNAs in Epithelial Ovarian Cancer. Noncoding RNA 2024, 10(5):51.
  • [25]Donati B, Lorenzini E, Ciarrocchi A. BRD4 and Cancer: Going beyond transcriptional regulation. Mol. Cancer 2018, 17(1):164.
  • [26]Li X, Yang L, Chen LL. The Biogenesis, Functions, and Challenges of Circular RNAs. Mol. Cell 2018, 71(3):428–442.
  • [27]Hu Q, Zhou T. EIciRNA-mediated gene expression: tunability and bimodality. FEBS Lett. 2018, 592(20):3460–3471.
  • [28]Mandel P MP. Les acides nucleiques du plasma sanguin chez l’ homme [The nucleic acids in blood plasma in humans]. CR Seances Soc Biol Fil 1948, 142:241–243.
  • [29]Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat. Rev. Clin. Oncol. 2013, 10(8):472–484.
  • [30]Stroun M, Anker P, Maurice P, Gahan PB. Circulating Nucleic Acids in Higher Organisms. Int. Rev. Cytol. 1977, 51:1–48.
  • [31]Stroun M, Anker P, Lyautey J, Lederrey C, Maurice PA. Isolation and characterization of DNA from the plasma of cancer patients. Eur. J. Cancer Clin. Oncol. 1987, 23(6):707–712.
  • [32]Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M. Origins, structures, and functions of circulating DNA in oncology. Cancer Metast. Rev. 2016, 35:347–376.
  • [33]Rashed MH, Bayraktar E, Helal GK, Abd-Ellah MF, Amero P, et al. Exosomes: From garbage bins to promising therapeutic targets. Int. J. Mol. Sci. 2017, 18(3):538.
  • [34]Schwarzenbach H, Gahan P. MicroRNA Shuttle from Cell-To-Cell by Exosomes and Its Impact in Cancer. Noncoding RNA 2019, 5(1):28.
  • [35]Krylova SV., Feng D. The Machinery of Exosomes: Biogenesis, Release, and Uptake. Int. J. Mol. Sci. 2023, 24(2):1337.
  • [36]Van Niel G, Porto-Carreiro I, Simoes S, Raposo G. Exosomes: A common pathway for a specialized function. J. Biochem. 2006, 140(1):13–21.
  • [37]Schwarzenbach H, Gahan PB. Predictive value of exosomes and their cargo in drug response/resistance of breast cancer patients. Cancer Drug Resistance 2020, 3(1):63–83.
  • [38]Li X, Li X, Zhang B, He B. The Role of Cancer Stem Cell-Derived Exosomes in Cancer Progression. Stem Cells Int. 2022, 2022(1):9133658.
  • [39]Chen J, Zhang G, Wan Y, Xia B, Ni Q, et al. Immune cell-derived exosomes as promising tools for cancer therapy. J. Controlled Release 2023, 364:508–528.
  • [40]Schwarzenbach H, Gahan PB. Exosomes in immune regulation. Noncoding RNA 2021, 7(1):4.
  • [41]Guo W, Qiao T, Dong B, Li T, Liu Q, et al. The Effect of Hypoxia-Induced Exosomes on Anti-Tumor Immunity and Its Implication for Immunotherapy. Front Immunol. 2022, 13:915985.
  • [42]Liu Y, Li X, Zhang T, Liu G. The Roles of Exosomes in Ovarian Cancer Chemo-resistance. J. Cancer 2023, 14(11):2128–2144.
  • [43]Chen C, Ma Z, Jiang H. EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells. Technol. Cancer Res. Treat. 2021, 20: 15330338211033077.
  • [44]Han QF, Li WJ, Hu KS, Gao J, Zhai WL, et al. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer. Mol. Cancer 2022, 21(1):207.
  • [45]Nigam SK. What do drug transporters really do? Nat. Rev. Drug Discov. 2015, 14(1):29–44.
  • [46]Vasiliou V, Vasiliou K, Nebert DW. Human ATP-binding cassette (ABC) transporter family. Hum. Genomics 2008, 3:281.
  • [47]Hrabeta J, Adam V, Eckschlager T, Frei E, Stiborova M, et al Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance. Anticancer Agents Med. Chem. 2016, 16(6):686–698.
  • [48]Nyce J. Drug-induced DNA Hypermethylation and Drug Resistance in Human Tumors. Cancer Res. 1989, 49(21): 5829–5836.
  • [49]Zhou J, Kang Y, Chen L, Wang H, Liu J, et al. The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents. Front Pharmacol. 2020, 11:343.
  • [50]Picard M. Management of Hypersensitivity Reactions to Taxanes. Immunol. Allergy Clin. North. Am. 2017, 37(4):679–693.
  • [51]Meredith AM, Dass CR. Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. J. Pharm. Pharmacol. 2016, 68(6):729–741.
  • [52]Li X, Li M, Huang M, Lin Q, Fang Q, et al. The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicine. Biomed. Pharmacother. 2022, 150:13064.
  • [53]Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat. Rev. Immunol. 2018;18(3):153–167.
  • [54]Chen MK, Liang ZJ, Luo DS, Xue KY, Liao DY, et al. Abiraterone, Orteronel, Enzalutamide and Docetaxel: Sequential or Combined Therapy? Front Pharmacol. 2022, 13:843110.
  • [55]Wu YL, Zhou C, Liam CK, Wu G, Liu X, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann. Oncol. 2015, 26(9):1883–1889.
  • [56]Tomar MS, Kumar A, Srivastava C, Shrivastava A. Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance. Biochim. Biophys. Acta Rev. Cancer 2021, 1876(2):188616.
  • [57]Tan CRC, Abdul-Majeed S, Cael B, Barta SK. Clinical Pharmacokinetics and Pharmacodynamics of Bortezomib. Clin. Pharmacokinet. 2018:157–168.
  • [58]Ebrahimi N, Fardi E, Ghaderi H, Palizdar S, Khorram R, Vafadar R, et al. Receptor tyrosine kinase inhibitors in cancer. Cell. Mol. Life Sci. 2023, 80(4):104.
  • [59]Xue C, Li G, Lu J, Li L. Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression. Signal Transduct Target Ther. 2021, 6(1):400.
  • [60]Xue C, Li G, Zheng Q, Gu X, Bao Z, et al. The functional roles of the circRNA/Wnt axis in cancer. Mol. Cancer 2022, 21(1):108.
  • [61]Farooqi AA, Naureen H, Attar R. Regulation of cell signaling pathways by circular RNAs and microRNAs in different cancers: Spotlight on Wnt/β-catenin, JAK/STAT, TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways. Semin. Cell. Dev. Biol. 2022, 124:72–81.
  • [62]Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, et al. The PI3K Pathway in Human Disease. Cell 2017, 170(4):605–635.
  • [63]Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal J. The PTEN/PI3K/AKT Signalling Pathway in Cancer, Therapeutic Implications. Curr. Cancer Drug Targets 2008, 8(3):187–198.
  • [64]Paplomata E, O’Regan R. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers. Ther. Adv. Med. Oncol. 2014, 6(4):154–166.
  • [65]Wang L, Yang X, Zhou F, Sun X, Li S. Circular RNA UBAP2 facilitates the cisplatin resistance of triple-negative breast cancer via microRNA-300/anti-silencing function 1B histone chaperone/PI3K/AKT/mTOR axis. Bioengineered 2022, 13(3):7197–7208.
  • [66]Li H, Xu W, Xia Z, Liu W, Pan G, et al. Hsa_circ_0000199 facilitates chemo-tolerance of triple-negative breast cancer by interfering with miR-206/613-led PI3K/Akt/mTOR signaling. Aging 2021, 13(3):4522–4551.
  • [67]Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell 2017, 169(6):985–999.
  • [68]Wu CI, Hoffman JA, Shy BR, Ford EM, Fuchs E et al. Function of Wnt/β-catenin in counteracting Tcf3 repression through the Tcf3–β-catenin interaction. Development 2012, 139(12):2118–2129.
  • [69]Ying Y, Tao Q. Epigenetic disruption of the WNT/ß-catenin signaling pathway in human cancers. Epigenetics 2009, 4(5):307–312.
  • [70]MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell 17(1): 9–26.
  • [71]Li J, Ma J, Huang S, Li J, Zhou L, et al. CircTTLL13 Promotes TMZ Resistance in Glioma via Modulating OLR1-Mediated Activation of the Wnt/β-Catenin Pathway. Mol. Cell Biol. 2023, 43(7):354–369.
  • [72]Zhou Q, Fu Q, Shaya M, Kugeluke Y, Li S, et al. Knockdown of circ_0055412 promotes cisplatin sensitivity of glioma cells through modulation of CAPG and Wnt/β-catenin signaling pathway. CNS Neurosci. Ther. 2022, 28(6):884–896.
  • [73]Dong L, Qu F. CircUBAP2 promotes SEMA6D expression to enhance the cisplatin resistance in osteosarcoma through sponging miR-506-3p by activating Wnt/β-catenin signaling pathway. J. Mol. Histol. 2020, 51(4):329–340.
  • [74]Hu X, li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct. Target. Ther. 2021, 6(1):402.
  • [75]Wang S, Cheng L, Wu H, Li G. Mechanisms and prospects of circular RNAs and their interacting signaling pathways in colorectal cancer. Front. Oncol. 2022, 12:949656.
  • [76]Brzozowa-Zasada M, Piecuch A, Michalski M, Segiet O, Kurek J, et al. Notch and its oncogenic activity in human malignancies. Eur. Surg. 2017, 49:199–209.
  • [77]Yao Y, Li X, Cheng L, Wu X, Wu B. Circular RNA FAT atypical cadherin 1 (circFAT1)/microRNA-525-5p/spindle and kinetochore-associated complex subunit 1 (SKA1) axis regulates oxaliplatin resistance in breast cancer by activating the notch and Wnt signaling pathway. Bioengineered 2021, 12(1):4032–4043.
  • [78]Calzado M, Bacher S, Schmitz ML. NF-κB Inhibitors for the Treatment of Inflammatory Diseases and Cancer. Curr. Med. Chem. 2007, 14(3):367–376.
  • [79]Ge L, Sun Y, Shi Y, Liu G, Teng F, et al. Plasma circRNA microarray profiling identifies novel circRNA biomarkers for the diagnosis of ovarian cancer. J. Ovarian Res. 2022, 15(1):58.
  • [80]Zhong AN, Yin Y, Tang BJ, Chen L, Shen HW, et al. CircRNA Microarray Profiling Reveals hsa_circ_0058493 as a Novel Biomarker for Imatinib-Resistant CML. Front. Pharmacol. 2021, 12:728916.
  • [81]Shao N, Song L, Sun X. Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis. Mol. Cell. Biochem. 2021, 476(6):2253–2267.
  • [82]Wang X, Wang H, Jiang H, Qiao L, Guo C. Circular RNAcirc_0076305 Promotes Cisplatin (DDP) Resistance of Non-Small Cell Lung Cancer Cells by Regulating ABCC1 Through miR-186-5p. Cancer Biother. Radiopharm. 2023, 38(5):293–304.
  • [83]Kun-Peng Z, Xiao-Long M, Chun-Lin Z. Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int. J. Biol. Sci. 2018, 14(3):321–330.
  • [84]Kunická T, Souček P. Importance of ABCC1 for cancer therapy and prognosis. Drug Metab. Rev. 2014, 46(3):325–342.
  • [85]Zhang Y, Tan X, Lu Y. Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis. J. Physiol. Biochem. 2022, 78(1):39–50.
  • [86]Saleban M, Harris EL, Poulter JA. D-Type Cyclins in Development and Disease. Genes 2023, 14(7):1445.
  • [87]Chen Y, Liu H, Zou J, Cao G, Li Y, et al. Exosomal circ_0091741 promotes gastric cancer cell autophagy and chemoresistance via the miR-330-3p/TRIM14/Dvl2/Wnt/β-catenin axis. Hum. Cell 2023, 36:258–275.
  • [88]Deng Y, Zhu H, Xiao L, Liu C, Meng X. Circ_0005198 Enhances Temozolomide Resistance of Glioma Cells Through Mir-198/Trim14 Axis. Aging 2021, 13(2):2198–2211.
  • [89]Xia W, Chen W, Ni C, Meng X, Wu J, et al. Chemotherapy-induced exosomal circBACH1 promotes breast cancer resistance and stemness via miR-217/G3BP2 signaling pathway. Breast Cancer Res. 2023, 25(1):85.
  • [90]Wu Y, Xu M, Feng Z, Wu H, Wu J, et al. AUF1-induced circular RNA hsa_circ_0010467 promotes platinum resistance of ovarian cancer through miR-637/LIF/STAT3 axis. Cell. Mol. Life Sci. 2023, 80(9):256.
  • [91]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.
  • [92]Ding J, Zhang X, Xue J, Fang L, Ban C, et al. CircNPM1 strengthens Adriamycin resistance in acute myeloid leukemia by mediating the miR-345-5p/FZD5 pathway. Cent. Eur. J. Immunol. 2021, 46:162–182.
  • [93]Xie H, Yao J, Wang Y, Ni B. Exosome-transmitted circVMP1 facilitates the progression and cisplatin resistance of non-small cell lung cancer by targeting miR-524-5p-METTL3/SOX2 axis. Drug Deliv. 2022, 29:1257–1271.
  • [94]Shi Q, Ji T, Ma Z, Tan Q, Liang J. Serum Exosomes-Based Biomarker circ_0008928 Regulates Cisplatin Sensitivity, Tumor Progression, and Glycolysis Metabolism by miR-488/HK2 Axis in Cisplatin-Resistant Nonsmall Cell Lung Carcinoma. Cancer Biother. Radiopharm. 2023, 38(8):558–571.
  • [95]Liu ZH, Yang SZ, Chen XT, Shao MR, Dong SY, et al. Correlations of hsa_circ_0046264 expression with onset, pathological stage and chemotherapy resistance of lung cancer. Eur. Rev. Med. Pharmacol. Sci. 2020, 24(18):9511–9521.
  • [96]Wang C, Xia S. Serum Hsa_circ_0005962 Is A Prognostic Biomarker of Paclitaxel Resistance in Nonsmall Cell Lung Cancer Treatment. Int. J. Clin. Pract. 2023, 2023(1):6644168.
  • [97]Chen SW, Zhu SQ, Pei X, Qiu BQ, Xiong D, et al. Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC. Mol. Cancer 2021, 20:144.
  • [98]Yang B, Teng F, Chang L, Wang J, Liu DL, et al. Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer. Aging 2021, 13(9):13264–13286.
  • [99]Zhang JW, Xu GY, Wang XF, Zhao YL, Kong QR. Circrna (Circ_0008057) promotes uremic serum-mediated proliferation and migration of vascular smooth muscle cells via mir-370/plk1 signaling pathway. J. Biol. Regul. Homeost. Agents 2021, 35(4).
  • [100]Chao F, Zhang Y, Lv L, Wei Y, Dou X, et al. Extracellular Vesicles Derived circSH3PXD2A Inhibits Chemoresistance of Small Cell Lung Cancer by miR-375-3p/YAP1. Int. J. Nanomedicine 2023, 18:2989–3006.
  • [101]Zhang Y, Chao F, Lv L, Li M, Shen Z. Hsa_circ_0041150 serves as a novel biomarker for monitoring chemotherapy resistance in small cell lung cancer patients treated with a first-line chemotherapy regimen. J. Cancer Res. Clin. Oncol. 2023, 149(17):15365–15382.
  • [102]Zou J, Lan H, Li W, Xie S, Tong Z, et al. Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients. Technol. Cancer Res. Treat. 2022, 21:15330338221139167.
  • [103]Li J, Zhu T, Weng Y, Cheng F, Sun Q, et al. Exosomal circDNER enhances paclitaxel resistance and tumorigenicity of lung cancer via targeting miR-139-5p/ITGB8. Thorac. Cancer 2022, 13(9):1381–1390.
  • [104]Gao J, Ao YQ, Zhang LX, Deng J, Wang S, et al. Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1. J. Exp. Clin. Canc. Res. 2022, 41(1):295.
  • [105]Hon KW, Ab-Mutalib NS, Abdullah NMA, Jamal R, Abu N. Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer. Sci. Rep. 2019, 9(1):16497.
  • [106]Hui B, Zhou C, Xu Y, Wang R, Dong Y, et al. Exosomes secreted by Fusobacterium nucleatum-infected colon cancer cells transmit resistance to oxaliplatin and 5-FU by delivering hsa_circ_0004085. J. Nanobiotechnology 2024, 22(1):62.
  • [107]Pan Z, Zheng J, Zhang J, Lin J, Lai J, et al. A Novel Protein Encoded by Exosomal CircATG4B Induces Oxaliplatin Resistance in Colorectal Cancer by Promoting Autophagy. Adv. Sci. 2022, 9(35):e2204513.
  • [108]Wang X, Zhang H, Yang H, Bai M, Ning T, et al. Exosome-delivered circRNA promotes glycolysis to induce chemoresistance through the miR-122-PKM2 axis in colorectal cancer. Mol. Oncol. 2020, 14(3):539–555.
  • [109]Yang G, Tan J, Guo J, Wu Z, Zhan Q. Exosome-mediated transfer of circ_0063526 enhances cisplatin resistance in gastric cancer cells via regulating miR-449a/SHMT2 axis. Anticancer Drug. 2022, 33(10):1047–1057.
  • [110]Yao W, Guo P, Mu Q, Wang Y. Exosome-Derived Circ-PVT1 Contributes to Cisplatin Resistance by Regulating Autophagy, Invasion, and Apoptosis Via miR-30a-5p/YAP1 Axis in Gastric Cancer Cells. Cancer Biother. Radiopharm. 2021, 36(4):347–359.
  • [111]Liang Q, Chu F, Zhang L, Jiang Y, Li L, et al. circ-LDLRAD3 Knockdown Reduces Cisplatin Chemoresistance and Inhibits the Development of Gastric Cancer with Cisplatin Resistance through miR-588 Enrichment-Mediated SOX5 Inhibition. Gut Liver 2023, 17(3):389–403.
  • [112]Zang X, Wang R, Wang Z, Qiu S, Zhang F, et al. Exosomal circ50547 as a potential marker and promotor of gastric cancer progression via miR-217/HNF1B axis. Transl. Oncol. 2024, 45:101969.
  • [113]Zhong Y, Wang D, Ding Y, Tian G, Jiang B. Circular RNA circ_0032821 contributes to oxaliplatin (OXA) resistance of gastric cancer cells by regulating SOX9 via miR-515-5p. Biotechnol. Lett. 2021, 43:339–351.
  • [114]Geng X, Zhang Y, Lin X, Zeng Z, Hu J, et al. Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma. Cell Death Dis. 2022, 13(7):596.
  • [115]Li X, Wang N, Leng H, Yuan H, Xu L. Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma. Metab. Brain Dis. 2022, 37(8):2979–2993.
  • [116]Han C, Wang S, Wang H, Zhang J. Exosomal circ-HIPK3 Facilitates Tumor Progression and Temozolomide Resistance by Regulating miR-421/ZIC5 Axis in Glioma. Cancer Biother. Radiopharm. 2021, 36(7):537–548.
  • [117]Si J, Li W, Li X, Cao L, Chen Z, et al. Heparanase confers temozolomide resistance by regulation of exosome secretion and circular RNA composition in glioma. Cancer Sci. 2021, 112(9):3491–3506.
  • [118]Tan WQ, Yuan L, Wu XY, He CG, Zhu SC, et al. Exosome-delivered circular RNA DLGAP4 induces chemoresistance via miR-143-HK2 axis in neuroblastoma. Cancer Biomarkers 2022, 34(3):375–384.
  • [119]Zhang PF, Gao C, Huang XY, Lu JC, Guo XJ, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol. Cancer 2020, 19:1–15.
  • [120]Zhang L, Xu T, Li Y, Pang Q, Ding X. Serum hsa_circ_0000615 is a prognostic biomarker of sorafenib resistance in hepatocellular carcinoma. J. Clin. Lab. Anal. 2022, 36(11):e24741.
  • [121]Lim MCJ, Baird AM, Greene J, McNevin C, Ronan K, et al. Hsa_circ_0001275 is one of a number of circRNAs dysregulated in enzalutamide resistant prostate cancer and confers enzalutamide resistance in vitro. Cancers 2021, 13(24):6383.
  • [122]Tan X, Song X, Fan B, Li M, Zhang A, et al. Exosomal circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) enhances the docetaxel resistance of prostate cancer via the microRNA-136-5p/tribbles homolog 1 pathway. Anticancer Drug. 2022, 33(9):871–882.
  • [123]Tao W, Luo ZH, He Y Di, Wang BY, Xia TL, et al. Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer. Br. J. Cancer 2023, 128(7):1320–1332.
  • [124]Zeng Z, Zhao Y, Chen QY, Zhu S, Niu Y, et al. Hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic pancreatic cancer cells via enhancing glycolysis. Oncogene 2021, 40(36):5505–5517.
  • [125]Pan Y, Lin Y, Mi C. Cisplatin-resistant osteosarcoma cell-derived exosomes confer cisplatin resistance to recipient cells in an exosomal circ_103801-dependent manner. Cell Biol. Int. 2021, 45(4):858–868.
  • [126]Wu X, Ren Y, Yao R, Zhou L, Fan R. Circular RNA circ-MMP11 Contributes to Lapatinib Resistance of Breast Cancer Cells by Regulating the miR-153-3p/ANLN Axis. Front. Oncol. 2021, 11:639961.
  • [127]Chen J, Wu S, Wang J, Sha Y, Ji Y. Hsa_circ_0074269-mediated Upregulation of TUFT1 Through miR-485-5p Increases Cisplatin Resistance in Cervical Cancer. Reprod. Sci. 2022, 29(8):2236–2250.
  • [128]Lin J, Qin H, Han Y, Li X, Zhao Y, et al. Circnrip1 modulates the mir-515-5p/il-25 axis to control 5-fu and cisplatin resistance in nasopharyngeal carcinoma. Drug Des. Devel. Ther. 2021, 15:323–330.
  • [129]Louis C, Ferlier T, Leroux R, Pineau R, Desoteux M, et al. TGFβ-induced circLTBP2 predicts a poor prognosis in intrahepatic cholangiocarcinoma and mediates gemcitabine resistance by sponging miR-338-3p. JHEP Reports 2023, 5(12):100900.
  • [130]Wang X, Cheng Q. Suppression of exosomal hsa_circ_0001005 eliminates the Vemurafenib resistance of melanoma. J. Cancer Res. Clin. Oncol. 2023, 149(9):5921–5936.
  • [131]Luo Y, Gui R. Circulating exosomal circmyc is associated with recurrence and bortezomib resistance in patients with multiple myeloma. Turk. J. Hematol. 2020, 37(4):248–262.
  • [132]Cao H xia, Miao C feng, Sang L na, Huang Y min, Zhang R, et al. Circ_0009910 promotes imatinib resistance through ULK1-induced autophagy by sponging miR-34a-5p in chronic myeloid leukemia. Life Sci. 2020, 243:117255.
  • [133]Solé C, Mentxaka G, Lawrie CH. The Use of circRNAs as Biomarkers of Cancer. Methods Mol. Biol. 2021, 2348:307–341.
  • [134]He AT, Liu J, Li F, Yang BB. Targeting circular RNAs as a therapeutic approach: current strategies and challenges. Signal Transduct. Target. Ther. 2021, 6(1):185.
  • [135]Schwarzenbach H. Potential of Exosomes as Therapeutics and Therapy Targets in Cancer Patients. Int. J. Transl. Med. 2024, 4(2):247–261.
  • [136]Hwang DW, Choi H, Jang SC, Yoo MY, Park JY, et al. Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO. Sci. Rep. 2015, 5(1):15636.
  • [137]Munagala R, Aqil F, Jeyabalan J, Kandimalla R, Wallen M, et al. Exosome-mediated delivery of RNA and DNA for gene therapy. Cancer Lett. 2021, 505:58–72.
  • [138]Yang Z, Xie J, Zhu J, Kang C, Chiang C, et al. Functional exosome-mimic for delivery of siRNA to cancer: in vitro and in vivo evaluation. J. Controlled Release 2016, 505:243.
  • [139]Choi Y, Yu A-M. ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development. Curr. Pharm. Des. 2014, 20(5):793–807.
  • [140]Liu Z, Dai Q, Yu X, Duan X, Wang C. Predicting circRNA-drug resistance associations based on a multimodal graph representation learning framework. IEEE J. Biomed. Health Inform. 2023, 1–11.
  • [141]Chen LL. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat. Rev. Mol. Cell Biol. 2020, 21(8):475–490.
  • [142]Wu P, Mo Y, Peng M, Tang T, Zhong Y, et al. Emerging role of tumor-related functional peptides encoded by lncRNA and circRNA. Mol. Cancer 2020, 19:1–14.
  • [143]Xu T, Wang L, Jia P, Song X, Zhao Z. An integrative transcriptomic and methylation approach for identifying differentially expressed circular rnas associated with dna methylation change. Biomedicines 2021, 9(6):657.
  • [144]Li S, Li X, Xue W, Zhang L, Yang LZ, et al. Screening for functional circular RNAs using the CRISPR–Cas13 system. Nat. Methods 2021, 18(1):51–59.
  • [145]Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021, 20(2):101–124.
Office Locations

Room 704, Cheuk Nang Centre, 9 Hillwood Road, Tsim Sha Tsui, Kowloon, Hong Kong

No.169th Liangui Road, Dongjing Street, Yuhua District, Changsha 410116, Hunan Province, China

Useful Links
About

ELSPublishing (ELSP) is an international publishing house dedicated to publishing high-quality journals, books, proceedings, and providing free conference system. ELSP is committed to promote scholarly communication and sharing, to build a globally integrated scholarly ecosystem, and to advance the cause for a wide range of scholars.

Website Copyright © 2024 ELSP