<?xml version="1.1" encoding="utf-8"?>
<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">PAR</journal-id><journal-title-group><journal-title>Proceedings of Anticancer Research</journal-title></journal-title-group><issn>2208-3545</issn><eissn>2208-3553</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/par.v8i2.6010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Research Progress of circRNAs during Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma</title><url>https://artdesignp.com/journal/PAR/8/2/10.26689/par.v8i2.6010</url><author>LiYuqing,RenCuicui,CaiYu,TianChang,JiaYuanyuan,WuGe</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>8</volume><issue>2</issue><history><date date-type="pub"><published-time>2024-03-28</published-time></date></history><abstract>Hepatocellular carcinoma is prone to invasion and metastasis. It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate. Epithelial-mesenchymal transformation (EMT) is a key factor in promoting tumor cell invasion and metastasis. Circular RNA (circRNA) is involved in regulating EMT in hepatocarcinoma cells through multiple pathways, thereby affecting the occurrence and progression of hepatocellular carcinoma. This article mainly reviews the research progress of circRNA related to EMT core transcription factors, circRNA that promotes EMT in liver cancer, and circRNA that inhibits EMT in liver cancer.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71(3): 209–249. https://doi.org/10.3322/caac.21660</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Zhou M, Wang H, Zeng X, et al., 2019, Mortality, Morbidity, and Risk Factors in China and Its Provinces, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet, 394(10204): 1145–1158. https://doi.org/10.1016/S0140-6736(19)30427-1</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Siegel RL, Miller KD, Jemal A, 2020, Cancer Statistics, 2020. CA Cancer J Clin, 70(1): 7–30. https://doi.org/10.3322/caac.21590</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Wang M, Wang Y, Feng X, et al., 2017, Contribution of Hepatitis B Virus and Hepatitis C Virus To Liver Cancer in China North Areas: Experience of the Chinese National Cancer Center. Int J Infect Dis, 65: 15–21. https://doi.org/10.1016/j.ijid.2017.09.003</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>Wang T, Chen D, 2021, Clinical Diagnosis and Treatment of Hepatocellular Carcinoma: From Guidelines to Clinical Practice. Journal of Clinical Hepatology, 37(8): 1745–1747. https://doi.org/10.3969/j.issn.1001-5256.2021.08.001</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Li X, Yang L, Chen L-L, 2018, The Biogenesis, Functions, and Challenges of Circular RNAs. Mol Cell, 71(3): 428–442. https://doi.org/10.1016/j.molcel.2018.06.034</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Rybak-Wolf A, Stottmeister C, Glažar P, et al., 2015, Circular RNAs in the Mammalian Brain are Highly Abundant, Conserved, and Dynamically Expressed. Mol Cell, 58(5): 870–885. https://doi.org/10.1016/j.molcel.2015.03.027</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Li Z, Huang C, Bao C, et al., 2015, Exon-Intron Circular RNAs Regulate Transcription in the Nucleus. Nat Struct Mol Biol, 22: 256–264. https://doi.org/10.1038/nsmb.2959</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Meng X, Li X, Zhang P, et al., 2017, Circular RNA: An Emerging Key Player in RNA World. Brief Bioinform, 18(4): 547–557. https://doi.org/10.1093/bib/bbw045</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Li J, Yang J, Zhou P, et al., 2015, Circular RNAs in Cancer: Novel Insights into Origins, Properties, Functions and Implications. Am J Cancer Res, 5(2): 472–480.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Pamudurti NR, Bartok O, Jens M, et al., 2017, Translation of CircRNAs. Mol Cell, 66(1): 9–21.e7. https://doi.org/10.1016/j.molcel.2017.02.021</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Huang A, Zheng H, Wu Z, et al., 2020, Circular RNA-Protein Interactions: Functions, Mechanisms, and Identification. Theranostics, 10(8): 3503–3517. https://doi.org/10.7150/thno.42174</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>Memczak S, Jens M, Elefsinioti A, et al., 2013, Circular RNAs are a Large Class of Animal RNAs with Regulatory Potency. Nature, 495(7441): 333–338. https://doi.org/10.1038/nature11928</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Chen B, Huang S, 2018, Circular RNA: An Emerging Non-Coding RNA as a Regulator and Biomarker in Cancer. Cancer Letters, 418: 41–50. https://doi.org/10.1016/j.canlet.2018.01.011</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>Dongre A, Weinberg RA, 2019, New Insights into the Mechanisms of Epithelial-Mesenchymal Transition and Implications for Cancer. Nat Rev Mol Cell Biol, 20(2): 69–84. https://doi.org/10.1038/s41580-018-0080-4</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Zhang CL, Tan XS, Huang ZS, 2021, Effect of Oxymatrine on Epithelial-Mesenchymal Transition and Cell Biological Characteristics of Human Hepatoma Carcinoma Cell Line Hepg2 by Upregulating Mir-204. Journal of Youjiang Medical University for Nationalities, 43(1): 11–16.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>Ou H, Chen Z, Xiang L, et al., 2019, Frizzled 2-Induced Epithelial-Mesenchymal Transition Correlates with Vasculogenic Mimicry, Stemness, and Hippo Signaling in Hepatocellular Carcinoma. Cancer Sci, 110(4): 1169–1182. https://doi.org/10.1111/cas.13949</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Giannelli G, Koudelkova P, Dituri F, et al., 2016, Role of Epithelial to Mesenchymal Transition in Hepatocellular Carcinoma. J Hepatol, 65(4): 798–808. https://doi.org/10.1016/j.jhep.2016.05.007</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Peinado H, Olmeda D, Cano A, 2007, Snail, Zeb and bHLH Factors in Tumour Progression: An Alliance Against the Epithelial Phenotype? Nat Rev Cancer, 7(6): 415–428. https://doi.org/10.1038/nrc2131</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B20" content-type="article"><label>20</label><element-citation publication-type="journal"><p>Yan L, 2020, The Role of CircCYP24A1 in HBx Induced Epithelial-Mesenchymal Transition and Tumor Invasion and Metastasis in Human Hepatocellular Carcinoma, thesis, China Medical University.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B21" content-type="article"><label>21</label><element-citation publication-type="journal"><p>Mo Z, Li R, Cao C, et al., 2023, Splicing Factor SNRPA Associated with Microvascular Invasion Promotes Hepatocellular Carcinoma Metastasis through Activating NOTCH1/Snail Pathway and is Mediated by circSEC62/miR-625-5p Axis. Environ Toxicol, 38(5): 1022–1037. https://doi.org/10.1002/tox.23745</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B22" content-type="article"><label>22</label><element-citation publication-type="journal"><p>Wang M, Yang Y, Yang J, et al., 2020, circ_KIAA1429 Accelerates Hepatocellular Carcinoma Advancement through the Mechanism of m6A-YTHDF3-Zeb1. Life Sci, 257: 118082. https://doi.org/10.1016/j.lfs.2020.118082</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B23" content-type="article"><label>23</label><element-citation publication-type="journal"><p>Meng J, Chen S, Han J-X, et al., 2018, Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma. Cancer Res, 78(15): 4150–4162. https://doi.org/10.1158/0008-5472.CAN-17-3009</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B24" content-type="article"><label>24</label><element-citation publication-type="journal"><p>Chen J, Qi Z, 2022, The Elevated circ_0067835 Could Accelerate Cell Proliferation and Metastasis via miR-1236-3p/Twist2 Axis in Hepatocellular Carcinoma. Biomed Res Int, 2022: 2825172. https://doi.org/1155/2022/2825172</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B25" content-type="article"><label>25</label><element-citation publication-type="journal"><p>Buchbinder EI, Desai A, 2016, CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol, 39(1): 98–106. https://doi.org/10.1097/COC.0000000000000239</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B26" content-type="article"><label>26</label><element-citation publication-type="journal"><p>Yang G, Wang X, Liu B, et al., 2019, circ-BIRC6, a Circular RNA, Promotes Hepatocellular Carcinoma Progression by Targeting the miR-3918/Bcl2 Axis. Cell Cycle, 18(9): 976–989. https://doi.org/10.1080/15384101.2019.1601477</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B27" content-type="article"><label>27</label><element-citation publication-type="journal"><p>Xu G, Zhang P, Liang H, et al., 2021, Circular RNA hsa_circ_0003288 Induces EMT and Invasion by Regulating hsa_circ_0003288/miR-145/PD-L1 Axis in Hepatocellular Carcinoma. Cancer Cell Int, 21(1): 212. https://doi.org/10.1186/s12935-021-01902-2</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B28" content-type="article"><label>28</label><element-citation publication-type="journal"><p>Taliaferro-Smith L, Oberlick E, Liu T, et al., 2015, FAK Activation is Required for IGF1R-Mediated Regulation of EMT, Migration, and Invasion in Mesenchymal Triple Negative Breast Cancer Cells. Oncotarget, 6(7): 4757–4772. https://doi.org/10.18632/oncotarget.3023</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B29" content-type="article"><label>29</label><element-citation publication-type="journal"><p>Kim HJ, Litzenburger BC, Cui X, et al., 2007, Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-?B and Snail. Mol Cell Biol, 27(8): 3165–3175. https://doi.org/10.1128/MCB.01315-06</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B30" content-type="article"><label>30</label><element-citation publication-type="journal"><p>Shen D, Zhao H, Zeng P, et al., 2022, Circular RNA circ_0001459 Accelerates Hepatocellular Carcinoma Progression via the miR-6165/IGF1R Axis. Ann N Y Acad Sci, 1512(1): 46–60. https://doi.org/10.1111/nyas.14753</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B31" content-type="article"><label>31</label><element-citation publication-type="journal"><p>Yu W, Jiang H, Zhang H, et al., 2018, hsa_circ_0003998 Promotes Cell Proliferation and Invasion by Targeting miR-326 in Non-Small Cell Lung Cancer. Onco Targets Ther, 11: 5569–5577. https://doi.org/10.2147/OTT.S174750</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B32" content-type="article"><label>32</label><element-citation publication-type="journal"><p>Tripathi V, Sixt KM, Gao S, et al., 2016, Direct Regulation of Alternative Splicing by SMAD3 through PCBP1 is Essential to the Tumor-Promoting Role of TGF-?. Mol Cell, 64(3): 549–564. https://doi.org/10.1016/h.molcel.2016.09.013</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B33" content-type="article"><label>33</label><element-citation publication-type="journal"><p>Yang L, Sun H, Liu X, et al., 2020, Circular RNA hsa_circ_0004277 Contributes to Malignant Phenotype of Colorectal Cancer by Sponging miR-512-5p to Upregulate the Expression of PTMA. J Cell Physiol, Early View. https://doi.org/10.1002/jcp.29484</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B34" content-type="article"><label>34</label><element-citation publication-type="journal"><p>Hsu Y-L, Hung J-Y, Chang W-A, et al., 2017, Hypoxic Lung Cancer-Secreted Exosomal miR-23a Increased Angiogenesis and Vascular Permeability by Targeting Prolyl Hydroxylase and Tight Junction Protein ZO-1. Oncogene, 36(34): 4929–4942. https://doi.org/10.1038/onc.2017.105</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B35" content-type="article"><label>35</label><element-citation publication-type="journal"><p>Zhu C, Su Y, Liu L, et al., 2021, Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells. Front Cell Dev Biol, 8: 585565. https://doi.org/10.3389/fcell.2020.585565</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B36" content-type="article"><label>36</label><element-citation publication-type="journal"><p>Wang S, Chai P, Jia R, et al., 2018, Novel Insights on m6A RNA Methylation in Tumorigenesis: A Double-Edged Sword. Mol Cancer, 17: 101. https://doi.org/10.1186/s12943-018-0847-4</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B37" content-type="article"><label>37</label><element-citation publication-type="journal"><p>Jiang C, Zeng X, Shan R, et al., 2020, The Emerging Picture of the Roles of circRNA-CDR1as in Cancer. Front Cell Dev Biol, 8: 590478. https://doi.org/10.3389/fcell.2020.590478</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B38" content-type="article"><label>38</label><element-citation publication-type="journal"><p>Yang X, Xiong Q, Wu Y, et al., 2017, Quantitative Proteomics Reveals the Regulatory Networks of Circular RNA CDR1as in Hepatocellular Carcinoma Cells. J Proteome Res, 16(10): 3891–3902. https://doi.org/10.1021/acs.jproteome.7b00519</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B39" content-type="article"><label>39</label><element-citation publication-type="journal"><p>Sun F, Wang JZ, Luo JJ, et al., 2018, miR-21 and miR-130b Targeted Artificial Modification of circRNA can Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells. China Medical Devices, 33(S1): 43–45.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B40" content-type="article"><label>40</label><element-citation publication-type="journal"><p>Shi Y, Sun X, He X, 2017, Overexpression of Aristaless-Like Homeobox-4 Inhibits Proliferation, Invasion, and EMT in Hepatocellular Carcinoma Cells. Oncol Res, 25(1): 11–18. https://doi.org/10.3727/096504016X14685034103833</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B41" content-type="article"><label>41</label><element-citation publication-type="journal"><p>Li M, Yue W, Li Q, et al., 2021, Circular RNA circ_0000098 Elevates ALX4 Expression via Adsorbing miR-1204 to Inhibit the Progression of Hepatocellular Carcinoma. Front Oncol, 11: 696078. https://doi.org/10.3389/fonc.2021.696078</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B42" content-type="article"><label>42</label><element-citation publication-type="journal"><p>Wang L, Tong X, Zhou Z, et al., 2018, Circular RNA hsa_circ_0008305 (circPTK2) Inhibits Tgf-?-Induced Epithelial-Mesenchymal Transition and Metastasis by Controlling TIF1? in Non-Small Cell Lung Cancer. Mol Cancer, 17(1): 140. https://doi.org/10.1186/s12943-018-0889-7</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B43" content-type="article"><label>43</label><element-citation publication-type="journal"><p>Wu SG, Zhou P, Chen JX, et al., 2021, circ-PTK2 (hsa_circ_0008305) Regulates the Pathogenic Processes of Ovarian Cancer via miR-639 and FOXC1 Regulatory Cascade. Cancer Cell Int, 21(1): 277. https://doi.org/10.1186/s12935-021-01985-x</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B44" content-type="article"><label>44</label><element-citation publication-type="journal"><p>Tsuchida A, Ohno S, Wu W, et al., 2011, miR-92 is a Key Oncogenic Component of the miR-17-92 Cluster in Colon Cancer. Cancer Sci, 102(12): 2264–2271. https://doi.org/10.1111/j.1349-7006.2011.02081.x</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B45" content-type="article"><label>45</label><element-citation publication-type="journal"><p>Gong T-T, Sun F-Z, Chen J-Y, et al., 2020, The Circular RNA circPTK2 Inhibits EMT in Hepatocellular Carcinoma by Acting as a ceRNA and Sponging miR-92a to Upregulate E-cadherin. Eur Rev Med Pharmacol Sci, 24(18): 9333–9342. https://doi.org/10.26355/eurrev_202009_23015</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
