Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Long Non-coding RNAs Regulating Macrophage Polarization in Liver Cancer

Author(s): Dengke Jia, Yaping He and Yawu Zhang*

Volume 30, Issue 27, 2024

Published on: 07 June, 2024

Page: [2120 - 2128] Pages: 9

DOI: 10.2174/0113816128311861240523075218

Price: $65

Abstract

Primary liver cancer is the second leading cause of cancer-related death worldwide. At present, liver cancer is often in an advanced stage once diagnosed, and treatment effects are generally poor. Therefore, there is an urgent need for other powerful treatments. Macrophages are an important component of the tumor microenvironment, and macrophage polarization is crucial to tumor proliferation and differentiation. Regulatory interactions between macrophage subtypes, such as M1 and M2, lead to a number of clinical outcomes, including tumor progression and metastasis. So, it is important to study the drivers of this process. Long non-coding RNA has been widely proven to be of great value in the early diagnosis and treatment of tumors. Many studies have shown that long non-coding RNA participates in macrophage polarization through its ability to drive M1 or M2 polarization, thereby participating in the occurrence and development of liver cancer. In this article, we systematically elaborated on the long non-coding RNAs involved in the polarization of liver cancer macrophages, hoping to provide a new idea for the early diagnosis and treatment of liver cancer. Liver cancer- related studies were retrieved from PubMed. Based on our identification of lncRNA and macrophage polarization as powerful therapies for liver cancer, we analyzed research articles in the PubMed system in the last ten years on the crosstalk between lncRNA and macrophage polarization. By targeting M1/M2 macrophage polarization, lncRNA may promote or suppress liver cancer, and the references are determined primarily by the article's impact factor. Consequently, the specific mechanism of action between lncRNA and M1/M2 macrophage polarization was explored, along with the role of their crosstalk in the occurrence, proliferation, and metastasis of liver cancer. LncRNA is bidirectionally expressed in liver cancer and can target macrophage polarization to regulate tumor behavior. LncRNA mainly functions as ceRNA and can participate in the crosstalk between liver cancer cells and macrophages through extracellular vesicles. LncRNA can potentially participate in the immunotherapy of liver cancer by targeting macrophages and becoming a new biomolecular marker of liver cancer.

« Previous Next »
[1]
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023; 73(1): 17-48.
[http://dx.doi.org/10.3322/caac.21763] [PMID: 36633525]
[2]
Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer 2020; 1873(1): 188314.
[http://dx.doi.org/10.1016/j.bbcan.2019.188314] [PMID: 31682895]
[3]
Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021; 7(1): 6.
[http://dx.doi.org/10.1038/s41572-020-00240-3] [PMID: 33479224]
[4]
Cheng K, Cai N, Zhu J, Yang X, Liang H, Zhang W. Tumor-associated macrophages in liver cancer: From mechanisms to therapy. Cancer Commun 2022; 42(11): 1112-40.
[http://dx.doi.org/10.1002/cac2.12345] [PMID: 36069342]
[5]
Li X, Ramadori P, Pfister D, Seehawer M, Zender L, Heikenwalder M. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat Rev Cancer 2021; 21(9): 541-57.
[http://dx.doi.org/10.1038/s41568-021-00383-9] [PMID: 34326518]
[6]
Ghafouri-Fard S, Abak A, Tavakkoli Avval S, Shoorei H, Taheri M, Samadian M. The impact of non-coding RNAs on macrophage polarization. Biomed Pharmacother 2021; 142: 112112.
[http://dx.doi.org/10.1016/j.biopha.2021.112112] [PMID: 34449319]
[7]
Cassetta L, Pollard JW. Targeting macrophages: Therapeutic approaches in cancer. Nat Rev Drug Discov 2018; 17(12): 887-904.
[http://dx.doi.org/10.1038/nrd.2018.169] [PMID: 30361552]
[8]
Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol 2020; 15(1): 123-47.
[http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012718] [PMID: 31530089]
[9]
Fendl B, Berghoff AS, Preusser M, Maier B. Macrophage and monocyte subsets as new therapeutic targets in cancer immunotherapy. ESMO Open 2023; 8(1): 100776.
[http://dx.doi.org/10.1016/j.esmoop.2022.100776] [PMID: 36731326]
[10]
Huang Z, Zhou JK, Peng Y, He W, Huang C. The role of long noncoding RNAs in hepatocellular carcinoma. Mol Cancer 2020; 19(1): 77.
[http://dx.doi.org/10.1186/s12943-020-01188-4] [PMID: 32295598]
[11]
Jiang P, Li X. Regulatory mechanism of lncRNAs in M1/M2 macrophages polarization in the diseases of different etiology. Front Immunol 2022; 13: 835932.
[http://dx.doi.org/10.3389/fimmu.2022.835932] [PMID: 35145526]
[12]
Xu Z, Chen Y, Ma L, et al. Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment. Mol Ther 2022; 30(10): 3133-54.
[http://dx.doi.org/10.1016/j.ymthe.2022.01.046] [PMID: 35405312]
[13]
Kadomoto S, Izumi K, Mizokami A. Macrophage polarity and disease control. Int J Mol Sci 2021; 23(1): 144.
[http://dx.doi.org/10.3390/ijms23010144] [PMID: 35008577]
[14]
Anderson NR, Minutolo NG, Gill S, Klichinsky M. Macrophage-based approaches for cancer immunotherapy. Cancer Res 2021; 81(5): 1201-8.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-2990] [PMID: 33203697]
[15]
Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity 2014; 41(1): 14-20.
[http://dx.doi.org/10.1016/j.immuni.2014.06.008] [PMID: 25035950]
[16]
Zhang J, Muri J, Fitzgerald G, et al. Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization. Cell Metab 2020; 31(6): 1136-1153.e7.
[http://dx.doi.org/10.1016/j.cmet.2020.05.004] [PMID: 32492393]
[17]
Sica A, Mantovani A. Macrophage plasticity and polarization: In vivo veritas. J Clin Invest 2012; 122(3): 787-95.
[http://dx.doi.org/10.1172/JCI59643] [PMID: 22378047]
[18]
Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 2017; 14(7): 399-416.
[http://dx.doi.org/10.1038/nrclinonc.2016.217] [PMID: 28117416]
[19]
Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010; 141(1): 39-51.
[http://dx.doi.org/10.1016/j.cell.2010.03.014] [PMID: 20371344]
[20]
Colegio OR, Chu NQ, Szabo AL, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 2014; 513(7519): 559-63.
[http://dx.doi.org/10.1038/nature13490] [PMID: 25043024]
[21]
Li X, Lei Y, Wu M, Li N. Regulation of macrophage activation and polarization by HCC-derived exosomal lncRNA TUC339. Int J Mol Sci 2018; 19(10): 2958.
[http://dx.doi.org/10.3390/ijms19102958] [PMID: 30274167]
[22]
Wang X, Zhou Y, Dong K, Zhang H, Gong J, Wang S. Exosomal lncRNA HMMR-AS1 mediates macrophage polarization through miR-147a/ARID3A axis under hypoxia and affects the progression of hepatocellular carcinoma. Environ Toxicol 2022; 37(6): 1357-72.
[http://dx.doi.org/10.1002/tox.23489] [PMID: 35179300]
[23]
Lee WJ, Shin CH, Ji H, et al. hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2. Cell Death Dis 2021; 12(4): 290.
[http://dx.doi.org/10.1038/s41419-021-03575-1] [PMID: 33731671]
[24]
Yu W, Wang S, Wang Y, et al. MicroRNA: Role in macrophage polarization and the pathogenesis of the liver fibrosis. Front Immunol 2023; 14: 1147710.
[http://dx.doi.org/10.3389/fimmu.2023.1147710] [PMID: 37138859]
[25]
Han C, Yang Y, Sheng Y, et al. The mechanism of lncRNA-CRNDE in regulating tumour-associated macrophage M2 polarization and promoting tumour angiogenesis. J Cell Mol Med 2021; 25(9): 4235-47.
[http://dx.doi.org/10.1111/jcmm.16477] [PMID: 33742511]
[26]
Nielsen MC, Hvidbjerg Gantzel R, Clària J, Trebicka J, Møller HJ, Grønbæk H. Macrophage activation markers, CD163 and CD206, in acute-on-chronic liver failure. Cells 2020; 9(5): 1175.
[http://dx.doi.org/10.3390/cells9051175] [PMID: 32397365]
[27]
Yu T, Gan S, Zhu Q, et al. Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24. Nat Commun 2019; 10(1): 4353.
[http://dx.doi.org/10.1038/s41467-019-12384-2] [PMID: 31554795]
[28]
Shi JH, Liu LN, Song DD, et al. TRAF3/STAT6 axis regulates macrophage polarization and tumor progression. Cell Death Differ 2023; 30(8): 2005-16.
[http://dx.doi.org/10.1038/s41418-023-01194-1] [PMID: 37474750]
[29]
Cheung K, Ma L, Wang G, et al. CD31 signals confer immune privilege to the vascular endothelium. Proc Natl Acad Sci USA 2015; 112(43): E5815-24.
[http://dx.doi.org/10.1073/pnas.1509627112]
[30]
Ye Y, Xu Y, Lai Y, et al. Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization. J Cell Biochem 2018; 119(3): 2951-63.
[http://dx.doi.org/10.1002/jcb.26509] [PMID: 29131381]
[31]
Carpenter S, Aiello D, Atianand MK, et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science 2013; 341(6147): 789-92.
[http://dx.doi.org/10.1126/science.1240925] [PMID: 23907535]
[32]
Ye Y, Wang M, Wang G, et al. LncRNA miR4458HG modulates hepatocellular carcinoma progression by activating m6A-dependent glycolysis and promoting the polarization of tumor-associated macrophages. Cell Mol Life Sci 2023; 80(4): 99.
[http://dx.doi.org/10.1007/s00018-023-04741-8] [PMID: 36933158]
[33]
Guo Y, Xie Y, Luo Y. The role of long non-coding RNAs in the tumor immune microenvironment. Front Immunol 2022; 13: 851004.
[http://dx.doi.org/10.3389/fimmu.2022.851004] [PMID: 35222443]
[34]
Lv S, Wang J, Li L. Extracellular vesicular lncRNA FAL1 promotes hepatocellular carcinoma cell proliferation and invasion by inducing macrophage M2 polarization. J Physiol Biochem 2023; 79(3): 669-82.
[http://dx.doi.org/10.1007/s13105-022-00922-4] [PMID: 37147492]
[35]
Li B, Mao R, Liu C, Zhang W, Tang Y, Guo Z. LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. Life Sci 2018; 197: 122-9.
[http://dx.doi.org/10.1016/j.lfs.2018.02.006] [PMID: 29421439]
[36]
Pai SG, Carneiro BA, Mota JM, et al. Wnt/beta-catenin pathway: Modulating anticancer immune response. J Hematol Oncol 2017; 10(1): 101.
[http://dx.doi.org/10.1186/s13045-017-0471-6] [PMID: 28476164]
[37]
Yang Y, Ye YC, Chen Y, et al. Crosstalk between hepatic tumor cells and macrophages via Wnt/β-catenin signaling promotes M2- like macrophage polarization and reinforces tumor malignant behaviors. Cell Death Dis 2018; 9(8): 793.
[http://dx.doi.org/10.1038/s41419-018-0818-0] [PMID: 30022048]
[38]
Chen J, Huang ZB, Liao CJ, et al. LncRNA TP73-AS1/miR-539/MMP-8 axis modulates M2 macrophage polarization in hepatocellular carcinoma via TGF-β1 signaling. Cell Signal 2020; 75: 109738.
[http://dx.doi.org/10.1016/j.cellsig.2020.109738] [PMID: 32818670]
[39]
Miao H, Lu J, Guo Y, et al. LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA-200a sponging. J Cell Mol Med 2021; 25(7): 3654-64.
[http://dx.doi.org/10.1111/jcmm.16425] [PMID: 33683827]
[40]
Yao H, Tian L, Yan B, Yang L, Li Y. LncRNA TP73-AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes. Cancer Cell Int 2022; 22(1): 16.
[http://dx.doi.org/10.1186/s12935-021-02418-5] [PMID: 35012518]
[41]
Wei Q, Liu G, Huang Z, et al. LncRNA MEG3 inhibits tumor progression by modulating macrophage phenotypic polarization via miR-145-5p/DAB2 axis in hepatocellular carcinoma. J Hepatocell Carcinoma 2023; 10: 1019-35.
[http://dx.doi.org/10.2147/JHC.S408800] [PMID: 37435155]
[42]
Park EG, Pyo SJ, Cui Y, Yoon SH, Nam JW. Tumor immune microenvironment lncRNAs. Brief Bioinform 2022; 23(1): bbab504.
[http://dx.doi.org/10.1093/bib/bbab504] [PMID: 34891154]
[43]
Price ZK, Lokman NA, Yoshihara M, Kajiyama H, Oehler MK, Ricciardelli C. Disabled-2 (DAB2): A key regulator of anti- and pro-tumorigenic pathways. Int J Mol Sci 2022; 24(1): 696.
[http://dx.doi.org/10.3390/ijms24010696] [PMID: 36614139]
[44]
Ji W, Bai J, Ke Y. Exosomal ZFPM2-AS1 contributes to tumorigenesis, metastasis, stemness, macrophage polarization, and infiltration in hepatocellular carcinoma through PKM mediated glycolysis. Environ Toxicol 2023; 38(6): 1332-46.
[http://dx.doi.org/10.1002/tox.23767] [PMID: 36880413]
[45]
Wang F, Zhang S, Vuckovic I, et al. Glycolytic stimulation is not a requirement for m2 macrophage differentiation. Cell Metab 2018; 28(3): 463-475.e4.
[http://dx.doi.org/10.1016/j.cmet.2018.08.012] [PMID: 30184486]
[46]
Cao M, Isaac R, Yan W, et al. Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth. Nat Cell Biol 2022; 24(6): 954-67.
[http://dx.doi.org/10.1038/s41556-022-00919-7] [PMID: 35637408]
[47]
Wang B, Li X, Hu W, Zhou Y, Din Y. Silencing of lncRNA SNHG20 delays the progression of nonalcoholic fatty liver disease to hepatocellular carcinoma via regulating liver Kupffer cells polarization. IUBMB Life 2019; 71(12): 1952-61.
[http://dx.doi.org/10.1002/iub.2137] [PMID: 31408278]
[48]
Zhu H, Zhao S, Jiao R, et al. Prognostic and clinicopathological significance of SNHG20 in human cancers: A meta-analysis. Cancer Cell Int 2020; 20(1): 304.
[http://dx.doi.org/10.1186/s12935-020-01403-8] [PMID: 32675944]
[49]
Xie Z, Xiang H, Li J, Zhang X, Li W, Tan G. SNHG20 promotes the development of laryngeal squamous cell carcinoma via miR-342-3p/MTDH axis. Heliyon 2022; 8(8): e10085.
[http://dx.doi.org/10.1016/j.heliyon.2022.e10085] [PMID: 36033309]
[50]
Zhou J, Che J, Xu L, Yang W, Zhou W, Zhou C. Tumor-derived extracellular vesicles containing long noncoding RNA PART1 exert oncogenic effect in hepatocellular carcinoma by polarizing macrophages into M2. Dig Liver Dis 2022; 54(4): 543-53.
[http://dx.doi.org/10.1016/j.dld.2021.07.005] [PMID: 34497040]
[51]
West AP, Brodsky IE, Rahner C, et al. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 2011; 472(7344): 476-80.
[http://dx.doi.org/10.1038/nature09973] [PMID: 21525932]
[52]
Xiang W, Shi R, Kang X, et al. Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression. Nat Commun 2018; 9(1): 2574.
[http://dx.doi.org/10.1038/s41467-018-04999-8] [PMID: 29968710]
[53]
Cao M, Yan H, Han X, et al. Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth. J Immunother Cancer 2019; 7(1): 326.
[http://dx.doi.org/10.1186/s40425-019-0817-4] [PMID: 31775862]
[54]
Sang L, Ju H, Yang Z, et al. Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress. Nat Metab 2021; 3(1): 90-106.
[http://dx.doi.org/10.1038/s42255-020-00325-z] [PMID: 33398195]
[55]
Wang X, Li F, Zhao W, et al. Long non-coding RNA GAS5 overexpression inhibits M2-like polarization of tumour-associated macrophages in SMCC-7721 cells by promoting PTEN expression. Int J Exp Pathol 2020; 101(6): 215-22.
[http://dx.doi.org/10.1111/iep.12374] [PMID: 33146930]
[56]
Wang X, Luo G, Zhang K, et al. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res 2018; 78(16): 4586-98.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3841] [PMID: 29880482]
[57]
Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell 2000; 100(4): 387-90.
[http://dx.doi.org/10.1016/S0092-8674(00)80674-1] [PMID: 10693755]
[58]
Pu J, Li W, Wang A, et al. Long non-coding RNA HOMER3-AS1 drives hepatocellular carcinoma progression via modulating the behaviors of both tumor cells and macrophages. Cell Death Dis 2021; 12(12): 1103.
[http://dx.doi.org/10.1038/s41419-021-04309-z] [PMID: 34815380]
[59]
Huang YH, Cai K, Xu PP, et al. CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis. Signal Transduct Target Ther 2021; 6(1): 10.
[http://dx.doi.org/10.1038/s41392-020-00437-8]
[60]
Pyonteck SM, Akkari L, Schuhmacher AJ, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med 2013; 19(10): 1264-72.
[http://dx.doi.org/10.1038/nm.3337] [PMID: 24056773]
[61]
Győri DS, Mócsai A. Osteoclast signal transduction during bone metastasis formation. Front Cell Dev Biol 2020; 8: 507.
[http://dx.doi.org/10.3389/fcell.2020.00507] [PMID: 32637413]
[62]
Yang J, Qu T, Li Y, Ma J, Yu H. Biological role of long non-coding RNA FTX in cancer progression. Biomed Pharmacother 2022; 153: 113446.
[http://dx.doi.org/10.1016/j.biopha.2022.113446] [PMID: 36076561]
[63]
Yang Y, Zhang J, Chen X, et al. LncRNA FTX sponges miR-215 and inhibits phosphorylation of vimentin for promoting colorectal cancer progression. Gene Ther 2018; 25(5): 321-30.
[http://dx.doi.org/10.1038/s41434-018-0026-7] [PMID: 29925853]
[64]
Jin S, He J, Zhou Y, Wu D, Li J, Gao W. LncRNA FTX activates FOXA2 expression to inhibit non–small-cell lung cancer proliferation and metastasis. J Cell Mol Med 2020; 24(8): 4839-49.
[http://dx.doi.org/10.1111/jcmm.15163] [PMID: 32176463]
[65]
Nawaz A, Bilal M, Fujisaka S, et al. Depletion of CD206+ M2- like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration. Nat Commun 2022; 13(1): 7058.
[http://dx.doi.org/10.1038/s41467-022-34191-y] [PMID: 36411280]
[66]
Paul S, Chhatar S, Mishra A, Lal G. Natural killer T cell activation increases iNOS+CD206- M1 macrophage and controls the growth of solid tumor. J Immunother Cancer 2019; 7(1): 208.
[http://dx.doi.org/10.1186/s40425-019-0697-7] [PMID: 31387637]
[67]
Wu H, Zhong Z, Wang A, et al. LncRNA FTX represses the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via regulating the M1/M2 polarization of Kupffer cells. Cancer Cell Int 2020; 20(1): 266.
[http://dx.doi.org/10.1186/s12935-020-01354-0] [PMID: 32595415]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy