Multiple roles of microRNA‑146a in immune responses and hepatocellular carcinoma (Review)
- Authors:
- Huihui Wang
- Xuemei Li
- Tao Li
- Lianzi Wang
- Xian Wu
- Jiaqing Liu
- Yuanhong Xu
- Wei Wei
-
Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Key Laboratory of Anti‑Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti‑Inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, P.R. China - Published online on: September 12, 2019 https://doi.org/10.3892/ol.2019.10862
- Pages: 5033-5042
-
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
|
Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Lagos-Quintana M, Rauhut R, Lendeckel W and Tuschl T: Identification of novel genes coding for small expressed RNAs. Science. 294:853–858. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Lau NC, Lim LP, Weinstein EG and Bartel DP: An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 294:858–862. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang H, Qu Y, Duan J, Deng T, Liu R, Zhang L, Bai M, Li J, Zhou L, Ning T, et al: Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer. Oncol Rep. 35:1135–1146. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Shi XB, Tepper CG and deVere White RW: Cancerous miRNAs and their regulation. Cell Cycle. 7:1529–1538. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS and Welch DR: Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res. 69:1279–1283. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Li Y, Vandenboom TG, Wang Z, Kong D, Ali S, Philip PA and Sarkar FH: miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 70:1486–1495. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Kogo R, Mimori K, Tanaka F, Komune S and Mori M: Clinical significance of miR-146a in gastric cancer cases. Clin Cancer Res. 17:4277–4284. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Labbaye C and Testa U: The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer. J Hematol Oncol. 5:132012. View Article : Google Scholar : PubMed/NCBI | |
|
Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T and Hammond SM: Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 20:2202–2207. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Taganov KD, Boldin MP, Chang KJ and Baltimore D: NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 103:12481–12486. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM and Lindsay MA: Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol. 180:5689–5698. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z and Cao X: MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1 and IRAK2. J Immunol. 183:2150–2158. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wu W and Li Y: Lung injury caused by paraquat poisoning results in increased interleukin-6 and decreased microRNA-146a levels. Exp Ther Med. 16:406–412. 2018.PubMed/NCBI | |
|
Peta E, Sinigaglia A, Masi G, Di Camillo B, Grassi A, Trevisan M, Messa L, Loregian A, Manfrin E, Brunelli M, et al: HPV16 E6 and E7 upregulate the histone lysine demethylase KDM2B through the c-MYC/miR-146a-5p axys. Oncogene. 37:1654–1668. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Cornett AL and Lutz CS: Regulation of COX-2 expression by miR-146a in lung cancer cells. RNA. 20:1419–1430. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Iacona JR, Monteleone NJ and Lutz CS: miR-146a suppresses 5-lipoxygenase activating protein (FLAP) expression and Leukotriene B4 production in lung cancer cells. Oncotarget. 9:26751–26769. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Batista PJ and Chang HY: Long noncoding RNAs: Cellular address codes in development and disease. Cell. 152:1298–1307. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Xi Y, Jiang T, Wang W, Yu J, Wang Y, Wu X and He Y: Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression. Sci Rep. 7:132342017. View Article : Google Scholar : PubMed/NCBI | |
|
Ding Y, Guo F, Zhu T, Li J, Gu D, Jiang W, Lu Y and Zhou D: Mechanism of long non-coding RNA MALAT1 in lipopolysaccharide-induced acute kidney injury is mediated by the miR-146a/NF-κB signaling pathway. Int J Mol Med. 41:446–454. 2018.PubMed/NCBI | |
|
Zhou YX, Zhao W, Mao LW, Wang YL, Xia LQ, Cao M, Shen J and Chen J: Long non-coding RNA NIFK-AS1 inhibits M2 polarization of macrophages in endometrial cancer through targeting miR-146a. Int J Biochem Cell Biol. 104:25–33. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Yu C, Shi D, Li Z, Wan G and Shi X: Long noncoding RNA CHRF exacerbates IL-6-induced inflammatory damages by downregulating microRNA-146a in ATDC5 cells. J Cell Physiol. 234:21851–21859. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Liu HT, Fang L, Cheng YX and Sun Q: LncRNA PVT1 regulates prostate cancer cell growth by inducing the methylation of miR-146a. Cancer Med. 5:3512–3519. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Kawai T and Akira S: The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat Immunol. 11:373–384. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K and Kimoto M: MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med. 189:1777–1782. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Meng J, Lien E and Golenbock DT: MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation. J Biol Chem. 285:8695–8702. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Guven-Maiorov E, Keskin O, Gursoy A, VanWaes C, Chen Z, Tsai CJ and Nussinov R: The architecture of the TIR domain signalosome in the toll-like receptor-4 signaling pathway. Sci Rep. 5:131282015. View Article : Google Scholar : PubMed/NCBI | |
|
Lin SC, Lo YC and Wu H: Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature. 465:885–890. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC and Flemington EK: Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol. 82:1946–1958. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Iwami KI, Matsuguchi T, Masuda A, Kikuchi T, Musikacharoen T and Yoshikai Y: Cutting edge: Naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol. 165:6682–6686. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao X, Huo R, Yan X and Xu T: IRF3 negatively regulates toll-like receptor-mediated NF-κB signaling by targeting TRIF for degradation in teleost fish. Front Immunol. 9:8672018. View Article : Google Scholar : PubMed/NCBI | |
|
Schorle H, Holtschke T, Hünig T, Schimpl A and Horak I: Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature. 352:621–624. 1991. View Article : Google Scholar : PubMed/NCBI | |
|
Curtale G, Citarella F, Carissimi C, Goldoni M, Carucci N, Fulci V, Franceschini D, Meloni F, Barnaba V and Macino G: An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood. 115:265–273. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Yang L, Boldin MP, Yu Y, Liu CS, Ea CK, Ramakrishnan P, Taganov KD, Zhao JL and Baltimore D: miR-146a controls the resolution of T cell responses in mice. J Exp Med. 209:1655–1670. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou L, Chong MM and Littman DR: Plasticity of CD4+ T cell lineage differentiation. Immunity. 30:646–655. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Murphy KM and Stockinger B: Effector T cell plasticity: Flexibility in the face of changing circumstances. Nat Immunol. 11:674–680. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Korn T, Bettelli E, Oukka M and Kuchroo VK: IL-17 and Th17 cells. Annu Rev Immunol. 27:485–517. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T, Yoshimura A, Baltimore D and Rudensky AY: Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell. 142:914–929. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Luo X, Han M, Liu J, Wang Y, Luo X, Zheng J, Wang S, Liu Z, Liu D, Yang PC and Li H: Epithelial cell-derived micro RNA-146a generates interleukin-10-producing monocytes to inhibit nasal allergy. Sci Rep. 5:159372015. View Article : Google Scholar : PubMed/NCBI | |
|
Okoye IS, Czieso S, Ktistaki E, Roderick K, Coomes SM, Pelly VS, Kannan Y, Perez-Lloret J, Zhao JL, Baltimore D, et al: Transcriptomics identified a critical role for Th2 cell-intrinsic miR-155 in mediating allergy and antihelminth immunity. Proc Natl Acad Sci USA. 111:E3081–E3090. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Hou T, Liao J, Zhang C, Sun C, Li X and Wang G: Elevated expression of miR-146, miR-139 and miR-340 involved in regulating Th1/Th2 balance with acute exposure of fine particulate matter in mice. Int Immunopharmacol. 54:68–77. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Li B, Wang X, Choi IY, Wang YC, Liu S, Pham AT, Moon H, Smith DJ, Rao DS, Boldin MP and Yang L: miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity. J Clin Invest. 127:3702–3716. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Pratama A, Srivastava M, Williams NJ, Papa I, Lee SK, Dinh XT, Hutloff A, Jordan MA, Zhao JL, Casellas R, et al: MicroRNA-146a regulates ICOS-ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres. Nat Commun. 6:64362015. View Article : Google Scholar : PubMed/NCBI | |
|
Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J, et al: miR-146a is a significant brake on autoimmunity, myeloproliferation and cancer in mice. J Exp Med. 208:1189–1201. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Cho S, Lee HM, Yu IS, Choi YS, Huang HY, Hashemifar SS, Lin LL, Chen MC, Afanasiev ND, Khan AA, et al: Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b. Nat Commun. 9:27572018. View Article : Google Scholar : PubMed/NCBI | |
|
Guo Q, Zhang J, Li J, Zou L, Zhang J, Xie Z, Fu X, Jiang S, Chen G, Jia Q, et al: Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells. Blood. 121:4875–4883. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Li Z, Zhang S, Wan Y, Cai M, Wang W, Zhu Y, Li Z, Hu Y, Wang H, Chen H, et al: MicroRNA-146a overexpression impairs the positive selection during T cell development. Front Immunol. 8:20062018. View Article : Google Scholar : PubMed/NCBI | |
|
King JK, Ung NM, Paing MH, Contreras JR, Alberti MO, Fernando TR, Zhang K, Pellegrini M and Rao DS: Regulation of marginal Zone B-cell differentiation by MicroRNA-146a. Front Immunol. 7:6702017. View Article : Google Scholar : PubMed/NCBI | |
|
Mao B and Wang G: MicroRNAs involved with hepatocellular carcinoma (Review). Oncol Rep. 34:2811–2820. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Li JF, Dai XP, Zhang W, Sun SH, Zeng Y, Zhao GY, Kou ZH, Guo Y, Yu H, Du LY, et al: Upregulation of microRNA-146a by hepatitis B virus X protein contributes to hepatitis development by downregulating complement factor H. MBio. 6:e02459–14. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Bandiera S, Pernot S, El Saghire H, Durand SC, Thumann C, Crouchet E, Ye T, Fofana I, Oudot MA, Barths J, et al: Hepatitis C virus-induced upregulation of MicroRNA miR-146a-5p in hepatocytes promotes viral infection and deregulates metabolic pathways associated with liver disease pathogenesis. J Virol. 90:6387–6400. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Visalli M, Bartolotta M, Polito F, Oteri R, Barbera A, Arrigo R, Di Giorgio RM, Navarra G and Aguennouz M: miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma. Int J Oncol. 53:771–780. 2018.PubMed/NCBI | |
|
Xu D, Han Q, Hou Z, Zhang C and Zhang J: miR-146a negatively regulates NK cell functions via STAT1 signaling. Cell Mol Immunol. 14:712–720. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang S, Zhang X, Ju Y, Zhao B, Yan X, Hu J, Shi L, Yang L, Ma Z, Chen L, et al: MicroRNA-146a feedback suppresses T cell immune function by targeting Stat1 in patients with chronic hepatitis B. J Immunol. 191:293–301. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Fattovich G, Stroffolini T, Zagni I and Donato F: Hepatocellular carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology. 127 (5 Suppl 1):S35–S50. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Qian H, Deng X, Huang ZW, Wei J, Ding CH, Feng RX, Zeng X, Chen YX, Ding J, Qiu L, et al: An HNF1α-regulated feedback circuit modulates hepatic fibrogenesis via the crosstalk between hepatocytes and hepatic stellate cells. Cell Res. 25:930–945. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Weiskirchen R and Tacke F: Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology. Hepatobiliary Surg Nutr. 3:344–363. 2014.PubMed/NCBI | |
|
Chen Y, Wu Z, Yuan B, Dong Y, Zhang L and Zeng Z: MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway. Cell Death Dis. 9:222018. View Article : Google Scholar : PubMed/NCBI | |
|
Lin A, Wang G, Zhao H, Zhang Y, Han Q, Zhang C, Tian Z and Zhang J: TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells. Oncoimmunology. 5:e10743762015. View Article : Google Scholar : PubMed/NCBI | |
|
Sun X, Zhang J, Hou Z, Han Q, Zhang C and Tian Z: miR-146a is directly regulated by STAT3 in human hepatocellular carcinoma cells and involved in anti-tumor immune suppression. Cell Cycle. 14:243–252. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu K, Pan Q, Zhang X, Kong LQ, Fan J, Dai Z, Wang L, Yang XR, Hu J, Wan JL, et al: miR-146a enhances angiogenic activity of endothelial cells in hepatocellular carcinoma by promoting PDGFRA expression. Carcinogenesis. 34:2071–2079. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Zhang Y, Sun XX, Ma X and Chen ZN: microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma. Mol Cancer. 14:52015. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou L, Zhao X, Han Y, Lu Y, Shang Y, Liu C, Li T, Jin Z, Fan D and Wu K: Regulation of UHRF1 by miR-146a/b modulates gastric cancer invasion and metastasis. FASEB J. 27:4929–4239. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H and Zhuang SM: A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis. 29:2126–2131. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Peng Q, Li S, Lao X, Chen Z, Li R, Deng Y and Qin X: The association of common functional polymorphisms in mir-146a and mir-196a2 and hepatocellular carcinoma risk: Evidence from a meta-analysis. Medicine (Baltimore). 93:e2522014. View Article : Google Scholar : PubMed/NCBI | |
|
Tian T, Wang M, Zhu W, Dai ZM, Lin S, Yang PT, Liu XH, Liu K, Zhu YY, Zheng Y, et al: miR-146a and miR-196a-2 polymorphisms are associated with hepatitis virus-related hepatocellular cancer risk: A meta-analysis. Aging (Albany NY). 9:381–392. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dong S, Miao AY, Lei W and Chen QW: miR-146a rs2910164 and hepatocellular carcinoma: A meta-analysis. Minerva Med. 108:287–292. 2017.PubMed/NCBI | |
|
Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR and de la Chapelle A: Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA. 105:7269–7274. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Moreno R and Berenguer M: Post-liver transplantation medical complications. Ann Hepatol. 5:77–85. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Hu J, Wang Z, Tan CJ, Liao BY, Zhang X, Xu M, Dai Z, Qiu SJ, Huang XW, Sun J, et al: Plasma microRNA, a potential biomarker for acute rejection after liver transplantation. Transplantation. 95:991–999. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhuo L, Liu J, Wang B, Gao M and Huang A: Differential miRNA expression profiles in hepatocellular carcinoma cells and drug-resistant sublines. Oncol Rep. 29:555–562. 2013. View Article : Google Scholar : PubMed/NCBI |
