摘要： miR-33a与脂质代谢、胰岛素抵抗、肝星状细胞活化有关,并且参与恶性肿瘤的发生和发展。miR-33a可以通过调节脂质代谢平衡来影响代谢相关脂肪性肝病(MAFLD)从脂肪性肝炎(MASH)到肝纤维化甚至肝癌的全过程,本文通过介绍miR-33a在MAFLD发生、发展过程中的重要作用,表明miR-33a有望成为MAFLD的一个强有力的治疗靶点。
方莹, 李武. miR-33a在代谢相关脂肪性肝病中的研究进展[J]. 肝脏, 2025, 30(5): 742-746.
| [1] 孔嘉宁,张彬彬,施军平. 《代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)》解读[J]. 临床肝胆病杂志, 2024, 40(9): 1767-1770. [2] Tian Y, Zhang M, Liu L X, et al. Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis[J]. Front Immunol, 2024, 15: 1400744. [3] Baselga-Escudero L, Arola-Arnal A, Pascual-Serrano A, et al. Chronic administration of proanthocyanidins or docosahexaenoic acid reverses the increase of miR-33a and miR-122 in dyslipidemic obese rats[J]. PLoS One, 2013, 8(7): e69817. [4] Kurylowicz A. MicroRNAs in human adipose tissue physiology and dysfunction[J]. Cells, 2021, 10(12). [5] Min H K, Kapoor A, Fuchs M, et al. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease[J]. Cell Metab, 2012, 15(5): 665-674. [6] Aryal B, Singh A K, Rotllan N, et al. MicroRNAs and lipid metabolism[J]. Curr Opin Lipidol, 2017, 28(3): 273-280. [7] Goedeke L, Salerno A, Ramirez C M, et al. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice[J]. EMBO Mol Med, 2014, 6(9): 1133-1141. [8] Tanoglu A, Cagiltay E, Tanoglu E G, et al. Circulating miR-200c and miR-33a may be used as biomarkers for predicting high fructose corn syrup-induced fatty liver and vitamin D supplementation-related liver changes[J]. Turk J Med Sci, 2022, 52(5): 1448-1457. [9] Tang T, Hu Y, Peng M, et al. Effects of high-fat diet on growth performance, lipid accumulation and lipid metabolism-related MicroRNA/gene expression in the liver of grass carp (Ctenopharyngodon idella)[J]. Comp Biochem Physiol B Biochem Mol Biol, 2019, 234: 34-40. [10] Li T, Francl J M, Boehme S, et al. Regulation of cholesterol and bile acid homeostasis by the cholesterol 7alpha-hydroxylase/steroid response element-binding protein 2/microRNA-33a axis in mice[J]. Hepatology, 2013, 58(3): 1111-1121. [11] Nie H, Yu X, He H, et al. Hepatocyte miR-33a mediates mitochondrial dysfunction and hepatosteatosis by suppressing NDUFA5[J]. J Cell Mol Med, 2018, 22(12): 6285-6293. [12] Ghareghani P, Shanaki M, Ahmadi S, et al. Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice[J]. Obes Res Clin Pract, 2018, 12(Suppl 2): 80-89. [13] 侯智为,刘艳霞, 李玉莹,等. miR-33a调控ABCA1表达介导棕榈酸诱导肝细胞脂质代谢损伤研究[J]. 临床军医杂志, 2019, 47(5): 522-524. [14] Stoica V C, Apostol D, Diculescu M M, et al. Time for micro-RNAs in steatotic liver disease: a case-control study[J]. Front Endocrinol (Lausanne), 2024, 15: 1349524. [15] Ono K, Horie T, Nishino T, et al. MicroRNA-33a/b in lipid metabolism - novel "thrifty" models[J]. Circ J, 2015, 79(2): 278-284. [16] Cerda A, Bortolin R H, Manriquez V, et al. Effect of statins on lipid metabolism-related microRNA expression in HepG2 cells[J]. Pharmacol Rep, 2021, 73(3): 868-880. [17] Zhang C, Chen K, Wei R, et al. The circFASN/miR-33a pathway participates in tacrolimus-induced dysregulation of hepatic triglyceride homeostasis[J]. Signal Transduct Target Ther, 2020, 5(1): 23. [18] Hu Y, Xu J, Chen Q, et al. Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats[J]. BMC Complement Med Ther, 2020, 20(1): 257. [19] Karimi-Sales E, Jeddi S, Ebrahimi-Kalan A, et al. Trans-chalcone prevents insulin resistance and hepatic inflammation and also promotes hepatic cholesterol efflux in high-fat diet-fed rats: modulation of miR-34a-, miR-451-, and miR-33a-related pathways[J]. Food Funct, 2018, 9(8): 4292-4298. [20] Jia L, Song N, Yang G, et al. Effects of tanshinone IIA on the modulation of miR-33a and the SREBP-2/Pcsk9 signaling pathway in hyperlipidemic rats[J]. Mol Med Rep, 2016, 13(6): 4627-4635. [21] Ma C, Zhang J, Yang S, et al. Astragalus flavone ameliorates atherosclerosis and hepatic steatosis via inhibiting lipid-disorder and inflammation in apoE(-/-) mice[J]. Front Pharmacol, 2020, 11: 610550. [22] Ortega R, Liu B, Persaud S J. Effects of miR-33 deficiency on metabolic and cardiovascular diseases: implications for therapeutic intervention[J]. Int J Mol Sci, 2023, 24(13). [23] Price N L, Zhang X, Fernandez-Tussy P, et al. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis[J]. Proc Natl Acad Sci U S A, 2021, 118(5):e2006478118. [24] Fernandez-Tussy P, Cardelo M P, Zhang H, et al. miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression[J]. JCI Insight, 2024, 9(19):e168476. [25] Erhartova D, Cahova M, Dankova H, et al. Serum miR-33a is associated with steatosis and inflammation in patients with non-alcoholic fatty liver disease after liver transplantation[J]. PLoS One, 2019, 14(11): e0224820. [26] Vega-Badillo J, Gutierrez-Vidal R, Hernandez-Perez H A, et al. Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects[J]. Liver Int, 2016, 36(9): 1383-1391. [27] Li Z J, Ou-Yang P H, Han X P. Profibrotic effect of miR-33a with Akt activation in hepatic stellate cells[J]. Cell Signal, 2014, 26(1): 141-148. [28] Tomita K, Teratani T, Suzuki T, et al. Free cholesterol accumulation in hepatic stellate cells: mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice[J]. Hepatology, 2014, 59(1): 154-169. [29] Liu H, Zhang S, Li Z, et al. Promotion of hepatic stellate cell activation and liver fibrosis by microRNA-33a-5p through targeting the Dickkopf-1-mediated wingless-related integration site/beta-catenin pathway[J]. J Physiol Pharmacol, 2023, 74(4): 431-449. [30] 蔡燕,黄俊琪. miR-33a抑制肝癌细胞的增殖、侵袭和迁移[J]. 中国生物化学与分子生物学报, 2017, 33(10): 1047-1053. [31] Chang W, Zhang L, Xian Y, et al. MicroRNA-33a promotes cell proliferation and inhibits apoptosis by targeting PPARalpha in human hepatocellular carcinoma[J]. Exp Ther Med, 2017, 13(5): 2507-2514. [32] 梅小平, 姚明, 周清河, 等. CRNDE介导miR-33a-5p/CDK6轴影响细胞周期调控人体肝癌细胞增殖的实验研究[J]. 浙江临床医学, 2023, 25(08): 1117-1120. [33] Han S Y, Han H B, Tian X Y, et al. MicroRNA-33a-3p suppresses cell migration and invasion by directly targeting PBX3 in human hepatocellular carcinoma[J]. Oncotarget, 2016, 7(27): 42461-42473. [34] Liu P, Chen B, Gu Y, et al. PNMA1, regulated by miR-33a-5p, promotes proliferation and EMT in hepatocellular carcinoma by activating the Wnt/beta-catenin pathway[J]. Biomed Pharmacother, 2018, 108: 492-499. [35] Li Y, Chen G, Yan Y, et al. CASC15 promotes epithelial to mesenchymal transition and facilitates malignancy of hepatocellular carcinoma cells by increasing TWIST1 gene expression via miR-33a-5p sponging[J]. Eur J Pharmacol, 2019, 860: 172589. [36] Ou H, Qian Y, Ma L. MCF2L-AS1 promotes the biological behaviors of hepatocellular carcinoma cells by regulating the miR-33a-5p/FGF2 axis[J]. Aging (Albany NY), 2023, 15(13): 6100-6116. [37] Xie R T, Cong X L, Zhong X M, et al. MicroRNA-33a downregulation is associated with tumorigenesis and poor prognosis in patients with hepatocellular carcinoma[J]. Oncol Lett, 2018, 15(4): 4571-4577. [38] 马智, 曹男, 李昶. 血清miR-122、miR-33a水平在老年原发性肝癌患者中的意义及其对TACE治疗预后的影响[J]. 国际检验医学杂志, 2022, 43(9): 1106-1110. [39] Hou H, Kang Y, Li Y, et al. miR-33a expression sensitizes Lgr5+ HCC-CSCs to doxorubicin via ABCA1[J]. Neoplasma, 2017, 64(1): 81-91. |
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