环状RNA特性及其在原发性肝癌中的研究进展
Characteristics of Circular RNA and Its Research Progress in Primary Liver Cancer
摘要: 原发性肝癌是一种常见的肝脏恶性肿瘤,发病率和死亡率较高,且由于早期难以被诊断,以致于错失有效治疗机会。环状RNA (circRNA)是内源性长链非编码RNA家族中的一员,因其具有稳定性,高度保守性和时间、空间特异性等特征,故其广泛累积表达于真核细胞的细胞质中。近年来发现circRNA在原发性肝癌的细胞增殖、凋亡、侵袭转移及预后等多方面发挥着巨大作用。目前circRNA已是继LncRNA后作为多种肿瘤早期诊断标志物和新治疗靶点的研究热点。本文对circRNA特征及其在原发性肝癌中的相关研究进展进行概述,以便于进一步探究其在原发性肝癌的临床诊疗过程中的潜在应用。
Abstract: Primary liver cancer is a common malignant liver tumor with high incidence rate and mortality rate. It is difficult to be diagnosed during its early stage, which leads to missed effective treatment. Circular RNA (circRNA) is a member of the endogenous long-chain noncoding RNA family. It is widely accumulated in the cytoplasm of eukaryotic cells because of its stability, high conservation, time and space specificity. In recent years, it has been found that circRNA plays an important role in proliferation, apoptosis, invasion, metastasis and prognosis of primary liver cancer. At present, after lncRNA, circRNA has become a research hotspot as a variety of tumor early diagnostic markers and new therapeutic targets. This paper aims to summarize the characteristics of circRNA and its related research progress in primary liver cancer, so as to further explore its potential application in the clinical diagnosis and treatment of primary liver cancer.
文章引用:陈芝涛, 黄佳程, 张乐乐, 万大龙, 林胜璋. 环状RNA特性及其在原发性肝癌中的研究进展[J]. 临床医学进展, 2020, 10(10): 2424-2431. https://doi.org/10.12677/ACM.2020.1010366

参考文献

[1] Bray, F., Ferlay, J., Soerjomataram, I., et al. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. [Google Scholar] [CrossRef] [PubMed]
[2] Chen, W., Zheng, R., Baade, P.D., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[3] Ashwal-Fluss, R., Meyer, M., Pamudurti, N.R., et al. (2014) circRNA Biogenesis Competes with Pre-mRNA Splicing. Molecular Cell, 56, 55-66. [Google Scholar] [CrossRef] [PubMed]
[4] Jeck, W.R. and Sharpless, N.E. (2014) Detecting and Characterizing Circular RNAs. Nature Biotechnology, 32, 453-461. [Google Scholar] [CrossRef] [PubMed]
[5] Jeck, W.R., Sorrentino, J.A., Wang, K., et al. (2013) Circular RNAs Are Abundant, Conserved, and Associated with ALU Repeats. RNA, 19, 141-157. [Google Scholar] [CrossRef] [PubMed]
[6] Zhang, X.O., Wang, H.B., Zhang, Y., et al. (2014) Complementary Sequence-Mediated Exon Circularization. Cell, 159, 134-147. [Google Scholar] [CrossRef] [PubMed]
[7] Ivanov, A., Memczak, S., Wyler, E., et al. (2015) Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals. Cell Reports, 10, 170-177. [Google Scholar] [CrossRef] [PubMed]
[8] Hansen, T.B., Jensen, T.I., Clausen, B.H., et al. (2013) Natural RNA Circles Function as Efficient microRNA Sponges. Nature, 495, 384-388. [Google Scholar] [CrossRef] [PubMed]
[9] Sanger, H.L., Klotz, G., Riesner, D., et al. (1976) Viroids Are Single-Stranded Covalently Closed Circular RNA Molecules Existing as Highly Base-Paired Rod-Like Structures. Proceedings of the National Academy of Sciences of the United States of America, 73, 3852-3856. [Google Scholar] [CrossRef] [PubMed]
[10] Rybak-Wolf, A., Stottmeister, C., Glazar, P., et al. (2015) Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. Molecular Cell, 58, 870-885. [Google Scholar] [CrossRef] [PubMed]
[11] Memczak, S., Jens, M., Elefsinioti, A., et al. (2013) Circular RNAs Are a Large Class of Animal RNAs with Regulatory Potency. Nature, 495, 333-338. [Google Scholar] [CrossRef] [PubMed]
[12] Li, X., Yang, L. and Chen, L.L. (2018) The Biogenesis, Functions, and Challenges of Circular RNAs. Molecular Cell, 71, 428-442. [Google Scholar] [CrossRef] [PubMed]
[13] Li, Y., Zheng, Q., Bao, C., et al. (2015) Circular RNA Is Enriched and Stable in Exosomes: A Promising Biomarker for Cancer Diagnosis. Cell Research, 25, 981-984. [Google Scholar] [CrossRef] [PubMed]
[14] You, X., Vlatkovic, I., Babic, A., et al. (2015) Neural Circular RNAs Are Derived from Synaptic Genes and Regulated by Development and Plasticity. Nature Neuroscience, 18, 603-610. [Google Scholar] [CrossRef] [PubMed]
[15] Bach, D.H. and Lee, S.K. (2018) Long Noncoding RNAs in Cancer Cells. Cancer Letters, 419, 152-166. [Google Scholar] [CrossRef] [PubMed]
[16] Bai, N., Peng, E., Qiu, X., et al. (2018) circFBLIM1 Act as a ceRNA to Promote Hepatocellular Cancer Progression by Sponging miR-346. Journal of Experimental & Clinical Cancer Research, 37, 172. [Google Scholar] [CrossRef] [PubMed]
[17] Li, Z., Huang, C., Bao, C., et al. (2017) Corrigendum: Exon-Intron Circular RNAs Regulate Transcription in the Nucleus. Nature Structural & Molecular Biology, 24, 194. [Google Scholar] [CrossRef] [PubMed]
[18] Guarnerio, J., Zhang, Y., Cheloni, G., et al. (2020) Intragenic Antagonistic Roles of Protein and circRNA in Tumorigenesis. Cell Research, 30, 188. [Google Scholar] [CrossRef] [PubMed]
[19] Hansen, T.B., Kjems, J. and Damgaard, C.K. (2013) Circular RNA and miR-7 in Cancer. Cancer Research, 73, 5609-5612. [Google Scholar] [CrossRef
[20] Du, W.W., Fang, L., Yang, W., et al. (2017) Induction of Tumor Apoptosis through a Circular RNA Enhancing Foxo3 Activity. Cell Death & Differentiation, 24, 357-370. [Google Scholar] [CrossRef] [PubMed]
[21] Dong, W., Dai, Z.H., Liu, F.C., et al. (2019) The RNA-Binding Protein RBM3 Promotes Cell Proliferation in Hepatocellular Carcinoma by Regulating Circular RNA SCD-circRNA 2 Production. EBioMedicine, 45, 155-167. [Google Scholar] [CrossRef] [PubMed]
[22] Chen, Y., Yang, F., Fang, E., et al. (2019) Circular RNA circAGO2 Drives Cancer Progression through Facilitating HuR-Repressed Functions of AGO2-miRNA Complexes. Cell Death & Differentiation, 26, 1346-1364. [Google Scholar] [CrossRef] [PubMed]
[23] Liang, W.C., Wong, C.W., Liang, P.P., et al. (2019) Translation of the Circular RNA circβ-catenin Promotes Liver Cancer Cell Growth through Activation of the Wnt Pathway. Genome Biology, 20, 84. [Google Scholar] [CrossRef] [PubMed]
[24] Tang, X., Zhu, J., Liu, Y., et al. (2019) Current Understanding of Circular RNAs in Gastric Cancer. Cancer Management and Research, 11, 10509-10521. [Google Scholar] [CrossRef
[25] Wang, H.Y., Wang, Y.P., Zeng, X., et al. (2020) Circular RNA Is a Popular Molecule in Tumors of the Digestive System (Review). International Journal of Oncology, 57, 21-42. [Google Scholar] [CrossRef] [PubMed]
[26] Sun, J.Y., Zhang, X.Y., Cao, Y.Z., et al. (2020) Diagnostic and Prognostic Value of Circular RNAs in Hepatocellular Carcinoma. Journal of Cellular and Molecular Medicine, 24, 5438-5445. [Google Scholar] [CrossRef] [PubMed]
[27] Fu, B., Zhang, A., Li, M., et al. (2018) Circular RNA Profile of Breast Cancer Brain Metastasis: Identification of Potential Biomarkers and Therapeutic Targets. Epigenomics, 10, 1619-1630. [Google Scholar] [CrossRef] [PubMed]
[28] Yang, X., Yuan, W., Tao, J., et al. (2017) Identification of Circular RNA Signature in Bladder Cancer. Journal of Cancer, 8, 3456-3463. [Google Scholar] [CrossRef] [PubMed]
[29] Han, D., Li, J., Wang, H., et al. (2017) Circular RNA circMTO1 Acts as the Sponge of microRNA-9 to Suppress Hepatocellular Carcinoma Progression. Hepatology, 66, 1151-1164. [Google Scholar] [CrossRef] [PubMed]
[30] Wang, Y., Qin, J., Liu, Q., et al. (2016) SNF2H Promotes Hepatocellular Carcinoma Proliferation by Activating the Wnt/beta-Catenin Signaling Pathway. Oncology Letters, 12, 1329-1336. [Google Scholar] [CrossRef] [PubMed]
[31] Yu, J., Xu, Q.G., Wang, Z.G., et al. (2018) Circular RNA cSMARCA5 Inhibits Growth and Metastasis in Hepatocellular Carcinoma. Journal of Hepatology, 68, 1214-1227. [Google Scholar] [CrossRef] [PubMed]
[32] Huang, X.Y., Huang, Z.L., Xu, Y.H., et al. (2017) Comprehensive Circular RNA Profiling Reveals the Regulatory Role of the circRNA-100338/miR-141-3p Pathway in Hepatitis B-Related Hepatocellular Carcinoma. Scientific Reports, 7, Article No. 5428. [Google Scholar] [CrossRef] [PubMed]
[33] Huang, X.Y., Huang, Z.L., Zhang, P.B., et al. (2019) CircRNA-100338 Is Associated with mTOR Signaling Pathway and Poor Prognosis in Hepatocellular Carcinoma. Frontiers in Oncology, 9, 392. [Google Scholar] [CrossRef] [PubMed]
[34] Huang, X.Y., Huang, Z.L., Huang, J., et al. (2020) Exosomal circRNA-100338 Promotes Hepatocellular Carcinoma Metastasis via Enhancing Invasiveness and Angiogenesis. Journal of Experimental & Clinical Cancer Research, 39, 20. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, X., Wang, X., Li, W., et al. (2019) Up-Regulation of hsa_circ_0000517 Predicts Adverse Prognosis of Hepatocellular Carcinoma. Frontiers in Oncology, 9, 1105. [Google Scholar] [CrossRef] [PubMed]
[36] He, S., Guo, Z., Kang, Q., et al. (2020) Circular RNA hsa_circ_0000517 Modulates Hepatocellular Carcinoma Advancement via the miR-326/SMAD6 Axis. Cancer Cell International, 20, 360. [Google Scholar] [CrossRef] [PubMed]
[37] He, S., Yang, J., Jiang, S., et al. (2020) Circular RNA circ_0000517 Regulates Hepatocellular Carcinoma Development via miR-326/IGF1R Axis. Cancer Cell International, 20, 404. [Google Scholar] [CrossRef] [PubMed]
[38] Forner, A., Reig, M. and Bruix, J. (2018) Hepatocellular Carcinoma. The Lancet, 391, 1301-1314. [Google Scholar] [CrossRef
[39] Juarez-Hernandez, E., Motola-Kuba, D., Chavez-Tapia, N.C., et al. (2017) Biomarkers in Hepatocellular Carcinoma: An Overview. Expert Review of Gastroenterology & Hepatology, 11, 549-558. [Google Scholar] [CrossRef] [PubMed]
[40] Wang, F., Nazarali, A.J. and Ji, S. (2016) Circular RNAs as Potential Biomarkers for Cancer Diagnosis and Therapy. American Journal of Cancer Research, 6, 1167-1176.
[41] Qu, S., Yang, X., Li, X., et al. (2015) Circular RNA: A New Star of Noncoding RNAs. Cancer Letters, 365, 141-148. [Google Scholar] [CrossRef] [PubMed]
[42] Wei, Y., Chen, X., Liang, C., et al. (2020) A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma. Hepatology, 71, 130-147. [Google Scholar] [CrossRef] [PubMed]
[43] Zhang, X., Zhou, H., Jing, W., et al. (2018) The Circular RNA hsa_circ_0001445 Regulates the Proliferation and Migration of Hepatocellular Carcinoma and May Serve as a Diagnostic Biomarker. Disease Markers, 2018, Article ID: 3073467. [Google Scholar] [CrossRef] [PubMed]
[44] Ju, Y., Hou, N., Meng, J., et al. (2010) T Cell Immunoglobulin- and Mucin-Domain-Containing Molecule-3 (Tim-3) Mediates Natural Killer Cell Suppression in Chronic Hepatitis B. Journal of Hepatology, 52, 322-329. [Google Scholar] [CrossRef] [PubMed]
[45] Sanchez-Correa, B., Lopez-Sejas, N., Duran, E., et al. (2019) Modulation of NK Cells with Checkpoint Inhibitors in the Context of Cancer Immunotherapy. Cancer Immunology, Immunotherapy, 68, 861-870. [Google Scholar] [CrossRef] [PubMed]
[46] Zhang, P.F., Gao, C., Huang, X.Y., et al. (2020) Cancer Cell-Derived Exosomal circUHRF1 Induces Natural Killer Cell Exhaustion and May Cause Resistance to Anti-PD1 Therapy in Hepatocellular Carcinoma. Molecular Cancer, 19, 110. [Google Scholar] [CrossRef] [PubMed]
[47] Li, Y., Zhai, Y., Song, Q., et al. (2018) Genome-Wide Association Study Identifies a New Locus at 7q21.13 Associated with Hepatitis B Virus-Related Hepatocellular Carcinoma. Clinical Cancer Research, 24, 906-915. [Google Scholar] [CrossRef
[48] Huang, X.Y., Zhang, P.F., Wei, C.Y., et al. (2020) Circular RNA circMET Drives Immunosuppression and Anti-PD1 Therapy Resistance in Hepatocellular Carcinoma via the miR-30-5p/snail/DPP4 Axis. Molecular Cancer, 19, 92. [Google Scholar] [CrossRef] [PubMed]
[49] Zhang, X., Qiu, S., Luo, P., et al. (2018) Down-Regulation of hsa_circ_0001649 in Hepatocellular Carcinoma Predicts a Poor Prognosis. Cancer Biomark, 22, 135-142. [Google Scholar] [CrossRef
[50] Wang, J., Tan, Q., Wang, W., et al. (2020) Mechanism of the Regulatory Effect of Overexpression of circMTO1 on Proliferation and Apoptosis of Hepatoma Cells via miR-9-5p/NOX4 Axis. Cancer Management and Research, 12, 3915-3925. [Google Scholar] [CrossRef