MicroRNAs as Modulators of Tumor Metabolism, Microenvironment, and Immune Response in Hepatocellular Carcinoma

References

• Petrick JL, McGlynn KA. The changing epidemiology of primary liver cancer. Curr Epidemiol Rep. 2019;6(2):104–111. doi:10.1007/s40471-019-00188-3
   PubMedGoogle Scholar
• Toffanin S, Hoshida Y, Lachenmayer A, et al. MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a. Gastroenterology. 2011;140(5):1618–28 e16. doi:10.1053/j.gastro.2011.02.009
   PubMed Web of Science ®Google Scholar
• Morishita A, Oura K, Tadokoro T, Fujita K, Tani J, Masaki T. MicroRNAs in the pathogenesis of hepatocellular carcinoma: a review. Cancers. 2021;13(3):514. doi:10.3390/cancers13030514
   PubMed Web of Science ®Google Scholar
• Fornari F, Milazzo M, Chieco P, et al. In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2. J Pathol. 2012;227(3):275–285. doi:10.1002/path.3995
   Web of Science ®Google Scholar
• Flor I, Bullerdiek J. The dark side of a success story: microRNAs of the C19MC cluster in human tumours. J Pathol. 2012;227(3):270–274. doi:10.1002/path.4014
   PubMed Web of Science ®Google Scholar
• Gramantieri L, Pollutri D, Gagliardi M, et al. MiR-30e-3p influences tumor phenotype through MDM2/TP53 axis and predicts sorafenib resistance in hepatocellular carcinoma. Cancer Res. 2020;80(8):1720–1734. doi:10.1158/0008-5472.CAN-19-0472
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi:10.1016/j.cell.2011.02.013
   PubMed Web of Science ®Google Scholar
• Warburg O. On respiratory impairment in cancer cells. Science. 1956;124(3215):269–270.
   PubMed Web of Science ®Google Scholar
• Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 2008;8(9):705–713. doi:10.1038/nrc2468
   PubMed Web of Science ®Google Scholar
• Kowalik MA, Guzzo G, Morandi A, et al. Metabolic reprogramming identifies the most aggressive lesions at early phases of hepatic carcinogenesis. Oncotarget. 2016;7(22):32375–32393. doi:10.18632/oncotarget.8632
   PubMedGoogle Scholar
• Chen Z, Lu W, Garcia-Prieto C, Huang P. The Warburg effect and its cancer therapeutic implications. J Bioenerg Biomembr. 2007;39(3):267–274. doi:10.1007/s10863-007-9086-x
   PubMed Web of Science ®Google Scholar
• Poff A, Koutnik AP, Egan KM, Sahebjam S, D’Agostino D, Kumar NB. Targeting the Warburg effect for cancer treatment: ketogenic diets for management of glioma. Semin Cancer Biol. 2019;56:135–148. doi:10.1016/j.semcancer.2017.12.011
   PubMed Web of Science ®Google Scholar
• Schwartz L, Seyfried T, Alfarouk KO, Da Veiga Moreira J, Fais S. Out of Warburg effect: an effective cancer treatment targeting the tumor specific metabolism and dysregulated pH. Semin Cancer Biol. 2017;43:134–138. doi:10.1016/j.semcancer.2017.01.005
   PubMed Web of Science ®Google Scholar
• Wang ZEK, Yang Q, Qin L, et al. A novel metabolism-related signature as a candidate prognostic biomarker for hepatocellular carcinoma. J Hepatocell Carcinoma. 2021;2021(8):119–132. doi:10.2147/JHC.S294108
   Web of Science ®Google Scholar
• Lai CY, Yeh KY, Lin CY, et al. MicroRNA-21 plays multiple oncometabolic roles in the process of NAFLD-related hepatocellular carcinoma via PI3K/AKT, TGF-beta, and STAT3 signaling. Cancers. 2021;13(5):940. doi:10.3390/cancers13050940
   PubMed Web of Science ®Google Scholar
• Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2):87–98. doi:10.1016/j.cmet.2006.01.005
   PubMed Web of Science ®Google Scholar
• Tsai WC, Hsu SD, Hsu CS, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Investig. 2012;122(8):2884–2897. doi:10.1172/JCI63455
   PubMed Web of Science ®Google Scholar
• Chai C, Rivkin M, Berkovits L, et al. Metabolic circuit involving free fatty acids, microRNA 122, and triglyceride synthesis in liver and muscle tissues. Gastroenterology. 2017;153(5):1404–1415. doi:10.1053/j.gastro.2017.08.013
   PubMed Web of Science ®Google Scholar
• Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. New Engl J Med. 2013;368(18):1685–1694. doi:10.1056/NEJMoa1209026
   PubMed Web of Science ®Google Scholar
• Burchard J, Zhang C, Liu AM, et al. microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. Mol Syst Biol. 2010;6(1):402. doi:10.1038/msb.2010.58
   Web of Science ®Google Scholar
• Liu AM, Xu Z, Shek FH, et al. miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma. PLoS One. 2014;9(1):e86872. doi:10.1371/journal.pone.0086872
   Web of Science ®Google Scholar
• Nie H, Li J, Yang XM, et al. Mineralocorticoid receptor suppresses cancer progression and the Warburg effect by modulating the miR-338-3p-PKLR axis in hepatocellular carcinoma. Hepatology. 2015;62(4):1145–1159. doi:10.1002/hep.27940
   Web of Science ®Google Scholar
• Li Q, Pan X, Zhu D, Deng Z, Jiang R, Wang X. Circular RNA MAT2B promotes glycolysis and malignancy of hepatocellular carcinoma through the miR-338-3p/PKM2 axis under hypoxic stress. Hepatology. 2019;70(4):1298–1316. doi:10.1002/hep.30671
   PubMed Web of Science ®Google Scholar
• Wang B, Hsu SH, Frankel W, Ghoshal K, Jacob ST. Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. Hepatology. 2012;56(1):186–197. doi:10.1002/hep.25632
   Web of Science ®Google Scholar
• Liu X, Liang Y, Song R, et al. Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation. Mol Cancer. 2018;17(1):90. doi:10.1186/s12943-018-0838-5
   PubMed Web of Science ®Google Scholar
• Nallamshetty S, Chan SY, Loscalzo J. Hypoxia: a master regulator of microRNA biogenesis and activity. Free Radic Biol Med. 2013;64:20–30. doi:10.1016/j.freeradbiomed.2013.05.022
   PubMed Web of Science ®Google Scholar
• Rane S, He M, Sayed D, et al. Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes. Circ Res. 2009;104(7):879–886. doi:10.1161/CIRCRESAHA.108.193102
   PubMed Web of Science ®Google Scholar
• Xu F, Yan JJ, Gan Y, et al. miR-885-5p negatively regulates warburg effect by silencing hexokinase 2 in liver cancer. Mol Ther Nucleic Acids. 2019;18:308–319. doi:10.1016/j.omtn.2019.09.002
   Google Scholar
• Callegari E, D’Abundo L, Guerriero P, et al. miR-199a-3p modulates MTOR and PAK4 pathways and inhibits tumor growth in a hepatocellular carcinoma transgenic mouse model. Mol Ther Nucleic Acids. 2018;11:485–493. doi:10.1016/j.omtn.2018.04.002
   PubMedGoogle Scholar
• Hou J, Lin L, Zhou W, et al. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 2011;19(2):232–243. doi:10.1016/j.ccr.2011.01.001
   PubMed Web of Science ®Google Scholar
• Guo W, Qiu Z, Wang Z, et al. MiR-199a-5p is negatively associated with malignancies and regulates glycolysis and lactate production by targeting hexokinase 2 in liver cancer. Hepatology. 2015;62(4):1132–1144. doi:10.1002/hep.27929
   PubMed Web of Science ®Google Scholar
• Zhang LF, Lou JT, Lu MH, et al. Suppression of miR-199a maturation by HuR is crucial for hypoxia-induced glycolytic switch in hepatocellular carcinoma. EMBO J. 2015;34(21):2671–2685. doi:10.15252/embj.201591803
   PubMed Web of Science ®Google Scholar
• Li B, He L, Zuo D, et al. Mutual regulation of MiR-199a-5p and HIF-1alpha modulates the warburg effect in hepatocellular carcinoma. J Cancer. 2017;8(6):940–949. doi:10.7150/jca.17496
   PubMed Web of Science ®Google Scholar
• Fornari F, Milazzo M, Chieco P, et al. MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2010;70(12):5184–5193. doi:10.1158/0008-5472.CAN-10-0145
   PubMed Web of Science ®Google Scholar
• Hua S, Lei L, Deng L, et al. miR-139-5p inhibits aerobic glycolysis, cell proliferation, migration, and invasion in hepatocellular carcinoma via a reciprocal regulatory interaction with ETS1. Oncogene. 2018;37(12):1624–1636. doi:10.1038/s41388-017-0057-3
   PubMed Web of Science ®Google Scholar
• Jin F, Wang Y, Zhu Y, et al. The miR-125a/HK2 axis regulates cancer cell energy metabolism reprogramming in hepatocellular carcinoma. Sci Rep. 2017;7(1):3089. doi:10.1038/s41598-017-03407-3
   Web of Science ®Google Scholar
• Jia YY, Zhao JY, Li BL, et al. miR-592/WSB1/HIF-1alpha axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth. Oncotarget. 2016;7(23):35257–35269. doi:10.18632/oncotarget.9135
   Google Scholar
• Komoll RM, Hu Q, Olarewaju O, et al. MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma. J Hepatol. 2021;74(1):122–134. doi:10.1016/j.jhep.2020.07.039
   PubMed Web of Science ®Google Scholar
• Budhu A, Jia HL, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology. 2008;47(3):897–907. doi:10.1002/hep.22160
   PubMed Web of Science ®Google Scholar
• Yang P, Li QJ, Feng Y, et al. TGF-beta-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012;22(3):291–303. doi:10.1016/j.ccr.2012.07.023
   PubMed Web of Science ®Google Scholar
• Zhou SL, Hu ZQ, Zhou ZJ, et al. miR-28-5p-IL-34-macrophage feedback loop modulates hepatocellular carcinoma metastasis. Hepatology. 2016;63(5):1560–1575. doi:10.1002/hep.28445
   PubMed Web of Science ®Google Scholar
• Wang L, Hu YY, Zhao JL, et al. Targeted delivery of miR-99b reprograms tumor-associated macrophage phenotype leading to tumor regression. J Immunother Cancer. 2020;8(2):e000517. doi:10.1136/jitc-2019-000517
   Web of Science ®Google Scholar
• Chen EB, Zhou ZJ, Xiao K, et al. The miR-561-5p/CX3CL1 signaling axis regulates pulmonary metastasis in hepatocellular carcinoma involving CX3CR1(+) natural killer cells infiltration. Theranostics. 2019;9(16):4779–4794. doi:10.7150/thno.32543
   PubMed Web of Science ®Google Scholar
• Zhang PF, Gao C, Huang XY, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol Cancer. 2020;19(1):110. doi:10.1186/s12943-020-01222-5
   PubMed Web of Science ®Google Scholar
• Zhou SL, Yin D, Hu ZQ, et al. A positive feedback loop between cancer stem-like cells and tumor-associated neutrophils controls hepatocellular carcinoma progression. Hepatology. 2019;70(4):1214–1230. doi:10.1002/hep.30630
   PubMed Web of Science ®Google Scholar
• Yan X, Zhang D, Wu W, et al. Mesenchymal stem cells promote hepatocarcinogenesis via lncRNA-MUF interaction with ANXA2 and miR-34a. Cancer Res. 2017;77(23):6704–6716. doi:10.1158/0008-5472.CAN-17-1915
   PubMed Web of Science ®Google Scholar
• Huang JL, Fu YP, Gan W, et al. Hepatic stellate cells promote the progression of hepatocellular carcinoma through microRNA-1246-RORalpha-Wnt/beta-Catenin axis. Cancer Lett. 2020;476:140–151. doi:10.1016/j.canlet.2020.02.012
   PubMed Web of Science ®Google Scholar
• Tian XP, Wang CY, Jin XH, et al. Acidic microenvironment up-regulates exosomal miR-21 and miR-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis. Theranostics. 2019;9(7):1965–1979. doi:10.7150/thno.30958
   PubMed Web of Science ®Google Scholar
• Zhou Y, Ren H, Dai B, et al. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts. J Exp Clin Cancer Res. 2018;37(1):324. doi:10.1186/s13046-018-0965-2
   PubMed Web of Science ®Google Scholar
• Fang T, Lv H, Lv G, et al. Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer. Nat Commun. 2018;9(1):191. doi:10.1038/s41467-017-02583-0
   PubMed Web of Science ®Google Scholar
• Fang JH, Zhang ZJ, Shang LR, et al. Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins. Hepatology. 2018;68(4):1459–1475. doi:10.1002/hep.29920
   PubMed Web of Science ®Google Scholar
• Omar HA, El-Serafi AT, Hersi F, et al. Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment. FEBS J. 2019;286(18):3540–3557. doi:10.1111/febs.15000
   PubMed Web of Science ®Google Scholar
• Jia L, Xi Q, Wang H, et al. miR-142-5p regulates tumor cell PD-L1 expression and enhances anti-tumor immunity. Biochem Biophys Res Commun. 2017;488(2):425–431. doi:10.1016/j.bbrc.2017.05.074
   PubMed Web of Science ®Google Scholar
• Lou K, Chen N, Li Z, et al. MicroRNA-142-5p overexpression inhibits cell growth and induces apoptosis by regulating FOXO in hepatocellular carcinoma cells. Oncol Res. 2017;25(1):65–73. doi:10.3727/096504016X14719078133366
   Web of Science ®Google Scholar
• Tsang FH, Au SL, Wei L, et al. MicroRNA-142-3p and microRNA-142-5p are downregulated in hepatocellular carcinoma and exhibit synergistic effects on cell motility. Front Med. 2015;9(3):331–343. doi:10.1007/s11684-015-0409-8
   PubMed Web of Science ®Google Scholar
• Zhao L, Yu H, Yi S, et al. The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget. 2016;7(29):45370–45384. doi:10.18632/oncotarget.9659
   PubMedGoogle Scholar
• Song N, Li P, Song P, et al. MicroRNA-138-5p suppresses non-small cell lung cancer cells by targeting PD-L1/PD-1 to regulate tumor microenvironment. Front Cell Dev Biol. 2020;8:540. doi:10.3389/fcell.2020.00540
   PubMed Web of Science ®Google Scholar
• Wei J, Nduom EK, Kong LY, et al. MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints. Neuro Oncol. 2016;18(5):639–648. doi:10.1093/neuonc/nov292
   Web of Science ®Google Scholar
• Li J, Shi W, Gao Y, et al. Analysis of microRNA expression profiles in human hepatitis B virus-related hepatocellular carcinoma. Clin Lab. 2013;59(9–10):1009–1015. doi:10.7754/Clin.Lab.2012.120901
   Web of Science ®Google Scholar
• Huang B, Li H, Huang L, Luo C, Zhang Y. Clinical significance of microRNA 138 and cyclin D3 in hepatocellular carcinoma. J Surg Res. 2015;193(2):718–723. doi:10.1016/j.jss.2014.03.076
   Web of Science ®Google Scholar
• Liu Y, Zhang W, Liu K, Liu S, Ji B, Wang Y. miR-138 suppresses cell proliferation and invasion by inhibiting SOX9 in hepatocellular carcinoma. Am J Transl Res. 2016;8(5):2159–2168.
   PubMed Web of Science ®Google Scholar
• Luo J, Chen P, Xie W, Wu F. MicroRNA-138 inhibits cell proliferation in hepatocellular carcinoma by targeting Sirt1. Oncol Rep. 2017;38(2):1067–1074. doi:10.3892/or.2017.5782
   PubMed Web of Science ®Google Scholar
• Liu W, Zheng X, Wang J, et al. MicroRNA-138 regulates T-cell function by targeting PD-1 in patients with hepatitis B virus-related liver diseases. Lab Med. 2021; epub ahed of print. doi:10.1093/labmed/lmaa110
   Web of Science ®Google Scholar
• Liu Y, Chen SH, Jin X, Li YM. Analysis of differentially expressed genes and microRNAs in alcoholic liver disease. Int J Mol Med. 2013;31(3):547–554. doi:10.3892/ijmm.2013.1243
   Web of Science ®Google Scholar
• Guo W, Tan W, Liu S, et al. MiR-570 inhibited the cell proliferation and invasion through directly targeting B7-H1 in hepatocellular carcinoma. Tumour Biol. 2015;36(11):9049–9057. doi:10.1007/s13277-015-3644-3
   Google Scholar
• Lin Y, Liu S, Su L, et al. miR-570 inhibits proliferation, angiogenesis, and immune escape of hepatocellular carcinoma. Cancer Biother Radiopharm. 2018;33(6):252–257. doi:10.1089/cbr.2017.2389
   Web of Science ®Google Scholar
• Fan F, Chen K, Lu X, Li A, Liu C, Wu B. Dual targeting of PD-L1 and PD-L2 by PCED1B-AS1 via sponging hsa-miR-194-5p induces immunosuppression in hepatocellular carcinoma. Hepatol Int. 2020; online ahed of print.
   Web of Science ®Google Scholar
• Chen L, Gibbons DL, Goswami S, et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014;5(1):5241. doi:10.1038/ncomms6241
   PubMed Web of Science ®Google Scholar
• Chen XM. MicroRNA signatures in liver diseases. World J Gastroenterol. 2009;15(14):1665–1672. doi:10.3748/wjg.15.1665
   PubMed Web of Science ®Google Scholar
• Wang X, Li J, Dong K, et al. Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal. 2015;27(3):443–452. doi:10.1016/j.cellsig.2014.12.003
   PubMed Web of Science ®Google Scholar
• Wrangle J, Wang W, Koch A, et al. Alterations of immune response of non-small cell lung cancer with azacytidine. Oncotarget. 2013;4(11):2067–2079. doi:10.18632/oncotarget.1542
   PubMed Web of Science ®Google Scholar
• Mao Y, Chen W, Wu H, Liu C, Zhang J, Chen S. Mechanisms and functions of MiR-200 family in hepatocellular carcinoma. Onco Targets Ther. 2020;13:13479–13490. doi:10.2147/OTT.S288791
   PubMed Web of Science ®Google Scholar
• Xie K, Liu J, Chen J, et al. Methylation-associated silencing of microRNA-34b in hepatocellular carcinoma cancer. Gene. 2014;543(1):101–107. doi:10.1016/j.gene.2014.03.059
   PubMed Web of Science ®Google Scholar
• Zhang HF, Wang YC, Han YD. MicroRNA34a inhibits liver cancer cell growth by reprogramming glucose metabolism. Mol Med Rep. 2018;17(3):4483–4489. doi:10.3892/mmr.2018.8399
   Web of Science ®Google Scholar
• Wei W, Tang H, Tang L. MicroRNA-34a inhibits metastasis in liver cancer cells. Oncol Lett. 2018;16(6):6960–6965. doi:10.3892/ol.2018.9555
   Web of Science ®Google Scholar
• Cortez MA, Ivan C, Valdecanas D, et al. PDL1 regulation by p53 via miR-34. J Natl Cancer Inst. 2016;108(1).
   PubMedGoogle Scholar
• Cheng B, Ding F, Huang CY, Xiao H, Fei FY, Li J. Role of miR-16-5p in the proliferation and metastasis of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2019;23(1):137–145. doi:10.26355/eurrev_201901_16757
   Web of Science ®Google Scholar
• Yang J, Liu R, Deng Y, et al. MiR-15a/16 deficiency enhances anti-tumor immunity of glioma-infiltrating CD8+ T cells through targeting mTOR. Int J Cancer. 2017;141(10):2082–2092. doi:10.1002/ijc.30912
   Web of Science ®Google Scholar
• Li Q, Johnston N, Zheng X, et al. miR-28 modulates exhaustive differentiation of T cells through silencing programmed cell death-1 and regulating cytokine secretion. Oncotarget. 2016;7(33):53735–53750. doi:10.18632/oncotarget.10731
   PubMedGoogle Scholar
• Tian Q, Xiao Y, Wu Y, et al. MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression. Int J Mol Med. 2016;38(5):1587–1595. doi:10.3892/ijmm.2016.2754
   Web of Science ®Google Scholar
• Boldrini L, Giordano M, Niccoli C, et al. Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma. Cancer Cell Int. 2017;17(1):105. doi:10.1186/s12935-017-0474-y
   Web of Science ®Google Scholar
• Zhu C, Zhao Y, Zhang Z, Ni Y, Li X, Yong H. MicroRNA-33a inhibits lung cancer cell proliferation and invasion by regulating the expression of beta-catenin. Mol Med Rep. 2015;11(5):3647–3651. doi:10.3892/mmr.2014.3134
   PubMed Web of Science ®Google Scholar
• Liu J, Fan L, Yu H, et al. Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages. Hepatology. 2019;70(1):241–258. doi:10.1002/hep.30607
   PubMed Web of Science ®Google Scholar
• Yin C, Han Q, Xu D, Zheng B, Zhao X, Zhang J. SALL4-mediated upregulation of exosomal miR-146a-5p drives T-cell exhaustion by M2 tumor-associated macrophages in HCC. Oncoimmunol. 2019;8(7):1601479. doi:10.1080/2162402X.2019.1601479
   PubMed Web of Science ®Google Scholar
• Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. New Engl J Med. 2020;382(20):1894–1905. doi:10.1056/NEJMoa1915745
   PubMed Web of Science ®Google Scholar
• Gramantieri L, Fornari F, Callegari E, et al. MicroRNA involvement in hepatocellular carcinoma. J Cell Mol Med. 2008;12(6A):2189–2204. doi:10.1111/j.1582-4934.2008.00533.x
   PubMed Web of Science ®Google Scholar
• Pollutri D, Gramantieri L, Bolondi L, Fornari F. TP53/MicroRNA interplay in hepatocellular carcinoma. Int J Mol Sci. 2016;17:12. doi:10.3390/ijms17122029
   Web of Science ®Google Scholar
• Fornari F, Gramantieri L, Callegari E, et al. MicroRNAs in animal models of HCC. Cancers. 2019;11(12):1906. doi:10.3390/cancers11121906
   Web of Science ®Google Scholar
• Hong DS, Kang YK, Borad M, et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br J Cancer. 2020;122(11):1630–1637. doi:10.1038/s41416-020-0802-1
   PubMed Web of Science ®Google Scholar
• van der Ree MH, de Vree JM, Stelma F, et al. Safety, tolerability, and antiviral effect of RG-101 in patients with chronic hepatitis C: a phase 1B, double-blind, randomised controlled trial. Lancet. 2017;389(10070):709–717. doi:10.1016/S0140-6736(16)31715-9
   PubMed Web of Science ®Google Scholar
• Reid G, Kao SC, Pavlakis N, et al. Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer. Epigenomics. 2016;8(8):1079–1085. doi:10.2217/epi-2016-0035
   PubMed Web of Science ®Google Scholar
• MacDiarmid JA, Mugridge NB, Weiss JC, et al. Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics. Cancer Cell. 2007;11(5):431–445. doi:10.1016/j.ccr.2007.03.012
   PubMed Web of Science ®Google Scholar