外泌体miRNAs在肝癌肿瘤免疫微环境中的研究进展

杨 净淇, 王 利荣, 李 飘, 刘 发林, 王 迪, 王 慧慧, 梅 士华, 郑 燕
湖北航天医院

摘要


肝脏是人类原发性癌症的常见部位，肝硬化和炎症一般是肝脏中发生的比较多的病症[1]。肝癌作为目前最常见的癌症之一，每年的发生率都在不断增长[2]。大多数肝细胞癌（HCC)在慢性肝炎的环境下进行转移和扩散，目前，microRNA（miRNA)正被当作预后和诊断的生物标志物，它还可以用来治疗癌症[3]。有研究表明，miRNA不仅可以作为丙型肝炎病毒感染的治疗剂，它还有一个潜在作用，就是能成为影响肝硬化和HCC发展的因素[4]。目前，miRNA已被证明参与几乎所有关键的细胞过程，如增殖、分化、迁移、凋亡等[5]，在这篇综述中，我们具体讨论了不同miRNA的特征，并讨论这些miRNA在癌症特别是肝癌中的作用，以及通过何种方式影响肝癌。

关键词


肝癌；免疫微环境；外泌体；miRNAs

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参考


[1] X. Li, P. Ramadori, D. Pfister, M. Seehawer, L. Zender, M. Heikenwalder, The immunological and metabolic landscape in primary and metastatic liver cancer, Nature Reviews Cancer 21 (2021) 541-557.

[2] D. Anwanwan, S.K. Singh, S. Singh, V. Saikam, R. Singh, Challenges in liver cancer and possible treatment approaches, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1873 (2020).

[3] D.M. Pereira, P.M. Rodrigues, P.M. Borralho, C.M.P. Rodrigues, Delivering the promise of miRNA cancer therapeutics, Drug Discovery Today 18 (2013) 282-289.

[4] R. Mohr, B. Özdirik, J. Lambrecht, M. Demir, J. Eschrich, L. Geisler, T. Hellberg, S.H. Loosen, T. Luedde, F. Tacke, L. Hammerich, C. Roderburg, From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis, International Journal of Molecular Sciences 22 (2021).

[5] L. Fabris, Y. Ceder, A.M. Chinnaiyan, G.W. Jenster, K.D. Sorensen, S. Tomlins, T. Visakorpi, G.A. Calin, The Potential of MicroRNAs as Prostate Cancer Biomarkers, European Urology 70 (2016) 312-322.

[6] C. He, S. Zheng, Y. Luo, B. Wang, Exosome Theranostics: Biology and Translational Medicine, Theranostics 8 (2018) 237-255.

[7] L. Doyle, M. Wang, Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis, Cells 8 (2019).

[8] X. Zhou, Z. Li, M. Qi, P. Zhao, Y. Duan, G. Yang, L. Yuan, Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice, Theranostics 10 (2020) 8197-8210.

[9] H. Wang, Z. Lu, X. Zhao, Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer, Journal of Hematology & Oncology 12 (2019).

[10] R.J. Simpson, J.W.E. Lim, R.L. Moritz, S. Mathivanan, Exosomes: proteomic insights and diagnostic potential, Expert Review of Proteomics 6 (2014) 267-283.

[11] H. Zhang, T. Deng, R. Liu, M. Bai, L. Zhou, X. Wang, S. Li, X. Wang, H. Yang, J. Li, T. Ning, D. Huang, H. Li, L. Zhang, G. Ying, Y. Ba, Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis, Nature Communications 8 (2017).

[12] B. Li, Y. Cao, M. Sun, H. Feng, Expression, regulation, and function of exosome‐derived miRNAs in cancer progression and therapy, The FASEB Journal 35 (2021).

[13] S. Lin, R.I. Gregory, MicroRNA biogenesis pathways in cancer, Nature Reviews Cancer 15 (2015) 321-333.

[14] M. Salehi, M. Sharifi, Exosomal miRNAs as novel cancer biomarkers: Challenges and opportunities, Journal of Cellular Physiology 233 (2018) 6370-6380.

[15] R.E. Drury, D. O’Connor, A.J. Pollard, The Clinical Application of MicroRNAs in Infectious Disease, Frontiers in Immunology 8 (2017).

[16] T. Fang, H. Lv, G. Lv, T. Li, C. Wang, Q. Han, L. Yu, B. Su, L. Guo, S. Huang, D. Cao, L. Tang, S. Tang, M. Wu, W. Yang, H. Wang, Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer, Nature Communications 9 (2018).

[17] G.A. Calin, C.D. Dumitru, M. Shimizu, Frequent deletions and down-regulation of microRNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia, (2002).

[18] S. Thakral, K. Ghoshal, miR-122 is a Unique Molecule with Great Potential in Diagnosis,Prognosis of Liver Disease, and Therapy Both as miRNA Mimic and Antimir, PubMed Central (2015).

[19] C. Jopling, Liver-specific microRNA-122: Biogenesis and function, RNA Biology 9 (2014) 137-142.

[20] Y. Seo, Y. Kang, Y. Ham, PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation, Proceedings of the National Academy of Sciences 119 (2022).

[21] K. Song, MiR-122 in hepatitis B virus and hepatitis C virus dual infection, World Journal of Hepatology 7 (2015).

[22] S. Bai, M.W. Nasser, B. Wang, S.-H. Hsu, J. Datta, H. Kutay, A. Yadav, G. Nuovo, P. Kumar, K. Ghoshal, MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to Sorafenib, Journal of Biological Chemistry 284 (2009) 32015-32027.

[23] H. Kutay, S. Bai, J. Datta, T. Motiwala, I. Pogribny, W. Frankel, S.T. Jacob, K. Ghoshal, Downregulation of miR‐122 in the rodent and human hepatocellular carcinomas, Journal of Cellular Biochemistry 99 (2006) 671-678.

[24] M. Panigrahi, M.A. Palmer, J.A. Wilson, MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication, Pathogens 11 (2022).

[25] G. Lou, X. Song, F. Yang, S. Wu, J. Wang, Z. Chen, Y. Liu, Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma, Journal of Hematology & Oncology 8 (2015).

[26] M. Khafaei, E. Rezaie, A. Mohammadi, P. Shahnazi Gerdehsang, S. Ghavidel, S. Kadkhoda, A. Zorrieh Zahra, N. Forouzanfar, H. Arabameri, M. Tavallaie, miR‐9: From function to therapeutic potential in cancer, Journal of Cellular Physiology 234 (2019) 14651-14665.

[27] M.-L. Chen, C.-G. Hong, T. Yue, H.-M. Li, R. Duan, W.-B. Hu, J. Cao, Z.-X. Wang, C.-Y. Chen, X.-K. Hu, B. Wu, H.-M. Liu, Y.-J. Tan, J.-H. Liu, Z.-W. Luo, Y. Zhang, S.-S. Rao, M.-J. Luo, H. Yin, Y.-Y. Wang, K. Xia, S.-Y. Tang, H. Xie, Z.-Z. Liu, Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer’s disease by enhancing autophagy, Theranostics 11 (2021) 2395-2409.

[28] F. Gao, Z.-L. Zhao, W.-T. Zhao, Q.-R. Fan, S.-C. Wang, J. Li, Y.-Q. Zhang, J.-W. Shi, X.-L. Lin, S. Yang, R.-Y. Xie, W. Liu, T.-T. Zhang, Y.-L. Sun, K. Xu, K.-T. Yao, D. Xiao, miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells, Biochemical and Biophysical Research Communications 431 (2013) 610-616.

[29] X. Li, Z. Zeng, J. Wang, Y. Wu, W. Chen, L. Zheng, T. Xi, A. Wang, Y. Lu, MicroRNA-9 and breast cancer, Biomedicine & Pharmacotherapy 122 (2020).

[30] E. Bandres, X. Agirre, N. Bitarte, N. Ramirez, R. Zarate, J. Roman‐Gomez, F. Prosper, J. Garcia‐Foncillas, Epigenetic regulation of microRNA expression in colorectal cancer, International Journal of Cancer 125 (2009) 2737-2743.

[31] D. Nass, S. Rosenwald, E. Meiri, S. Gilad, H. Tabibian-Keissar, A. Schlosberg, H. Kuker, N. Sion-Vardy, A. Tobar, O. Kharenko, E. Sitbon, G. Lithwick Yanai, E. Elyakim, H. Cholakh, H. Gibori, Y. Spector, Z. Bentwich, I. Barshack, N. Rosenfeld, MiR-92b and miR-9/9* Are Specifically Expressed in Brain Primary Tumors and Can Be Used to Differentiate Primary from Metastatic Brain Tumors, Brain Pathology 19 (2009) 375-383.

[32] H.C. Chen, G.H. Chen, Y.H. Chen, W.L. Liao, C.Y. Liu, K.P. Chang, Y.S. Chang, S.J. Chen, MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma, British Journal of Cancer 100 (2009) 1002-1011.

[33] C.-Y. Jia, W. Xiang, J.-B. Liu, G.-X. Jiang, F. Sun, J.-J. Wu, X.-L. Yang, R. Xin, Y. Shi, D.-D. Zhang, W. Li, Z. Zuberi, J. Zhang, G.-X. Lu, H.-M. Wang, P.-Y. Wang, F. Yu, Z.-W. Lv, Y.-S. Ma, D. Fu, MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer, Technology in Cancer Research & Treatment 20 (2021).

[34] T. Si, L. Huang, T. Liang, P. Huang, H. Zhang, M. Zhang, X. Zhou, Ruangan Lidan decoction inhibits the growth and metastasis of liver cancer by downregulating miR-9-5p and upregulating PDK4, Cancer Biology & Therapy 24 (2023).

[35] Z. Liu, J.Y. Chen, Y. Zhong, L. Xie, J.S. Li, lncRNA MEG3 inhibits the growth of hepatocellular carcinoma cells by sponging miR-9-5p to upregulate SOX11, Brazilian Journal of Medical and Biological Research 52 (2019).

[36] H. Hu, W. Huang, H. Zhang, J. Li, Q. Zhang, Y.-R. Miao, F.-F. Hu, L. Gan, Z. Su, X. Yang, A.-Y. Guo, A miR-9-5p/FOXO1/CPEB3 Feed-Forward Loop Drives the Progression of Hepatocellular Carcinoma, Cells 11 (2022).

[37] F.W. Xiao Dong, Ying Xue,ZhiPeng Lin, WeiFeng Song, Ning Yang and Qi Li, MicroRNA‑9‑5p downregulates Klf4 and influences the progression of hepatocellular carcinoma via the AKT signaling pathway, INTERNATIONAL JOURNAL OF MOlecular medicine 43: 1417-1429, 2019.

[38] Z. Shu, F. Gao, Q. Xia, M. Zhang, MiR-9-5p promotes cell proliferation and migration of hepatocellular carcinoma by targeting CPEB3, Future Science Group (2021).

[39] Surina, R.A. Fontanella, L. Scisciola, R. Marfella, G. Paolisso, M. Barbieri, miR-21 in Human Cardiomyopathies, Frontiers in Cardiovascular Medicine 8 (2021).

[40] S.M. Hammond, An overview of microRNAs, Advanced Drug Delivery Reviews 87 (2015) 3-14.

[41] P.P. Medina, M. Nolde, F.J. Slack, OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma, Nature 467 (2010) 86-90.

[42] M.E. Hatley, D.M. Patrick, M.R. Garcia, J.A. Richardson, R. Bassel-Duby, E. van Rooij, E.N. Olson, Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21, Cancer Cell 18 (2010) 282-293.

[43] Y.S. Feng, J.M. Zhou, C.H. Sun, J. Zhu, J. Yang, L. Guo, The diagnostic value of miR-21 combined with CT in patients with liver cancer, Clinical and Translational Oncology 23 (2020) 1238-1244.

[44] J. Zou, X. Zhu, D. Xiang, Y. Zhang, J. Li, Z. Su, L. Kong, H. Zhang, LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase, Acta Pharmaceutica Sinica B 11 (2021) 1578-1591.

[45] S. Ghafouri-Fard, H. Shoorei, Z. Bahroudi, A. Abak, J. Majidpoor, M. Taheri, An update on the role of miR-124 in the pathogenesis of human disorders, Biomedicine & Pharmacotherapy 135 (2021).

[46] E.A. Braga, M.V. Fridman, A.M. Burdennyy, E.A. Filippova, V.I. Loginov, I.V. Pronina, A.A. Dmitriev, N.E. Kushlinskii, Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs, International Journal of Molecular Sciences 23 (2022).

[47] Y. Feng, W. Jiang, W. Zhao, Z. Lu, Y. Gu, Y. Dong, miR-124 regulates liver cancer stem cells expansion and sorafenib resistance, Experimental Cell Research 394 (2020).

[48] H. Xiang, M. Luo, P. Hou, Z. Xiao, Z. Huang, Q. Feng, R. Zhang, Y. Li, L. Wu, miR-124-3p combined with miR-506-3p delay hepatic carcinogenesis via modulating sirtuin 1, Biomarkers 26 (2021) 196-206.

[49] T. Demir, S.S. Lee, A.O. Kaseb, Systemic therapy of liver cancer, Mechanisms and Therapy of Liver Cancer2021, pp. 257-294.

[50] Z.-b. Dong, H.-m. Wu, Y.-c. He, Z.-t. Huang, Y.-h. Weng, H. Li, C. Liang, W.-m. Yu, W. Chen, MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1, Cell Death & Disease 13 (2022).

[51] R. Sanuki, T. Yamamura, Tumor Suppressive Effects of miR-124 and Its Function in Neuronal Development, International Journal of Molecular Sciences 22 (2021).

[52] D. Zhong, X. Lyu, X. Fu, P. Xie, M. Liu, F. He, G. Huang, Upregulation of miR-124-3p by Liver X Receptor Inhibits the Growth of Hepatocellular Carcinoma Cells Via Suppressing Cyclin D1 and CDK6, Technology in Cancer Research & Treatment 19 (2020).

[53] S. Chen, L. Wang, J. Fan, C. Ye, D. Dominguez, Y. Zhang, T.J. Curiel, D. Fang, T.M. Kuzel, B. Zhang, Host miR155 Promotes Tumor Growth through a Myeloid-Derived Suppressor Cell–Dependent Mechanism, Cancer Research 75 (2015) 519-531.

[54] X. Xin, Y. Lu, S. Xie, Y. Chen, X. Jiang, S. Song, L. Wang, H. Pu, X. Gui, T. Li, J. Xu, J. Li, S. Jia, D. Lu, miR-155 Accelerates the Growth of Human Liver Cancer Cells by Activating CDK2 via Targeting H3F3A, Molecular Therapy - Oncolytics 17 (2020) 471-483.

[55] Q. Wang, G.-t. Wang, W.-h. Lu, MiR-155 Inhibits Malignant Biological Behavior of Human Liver Cancer Cells by Regulating SRPK1, Technology in Cancer Research & Treatment 20 (2021).

[56] X.A.W. Xue, Jing %A Fu, Ke %A Dai, Shu %A Wu, Rui %A Peng, Cheng %A Li, Yunxia, The role of miR-155 on liver diseases by modulating immunity, inflammation and tumorigenesis %J INTERNATIONAL IMMUNOPHARMACOLOGY, 116 (2023) null-null.

[57] Z. Chen, T. Ma, C. Huang, T. Hu, J. Li, The Pivotal Role of microRNA‐155 in the Control of Cancer, Journal of Cellular Physiology 229 (2014) 545-550.


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