王晓露
塔里木大学医学院基础医学系
摘要(Abstract):
真核生物翻译起始因子4A(eIF4A)家族由eIF4A1、eIF4A2和eIF4A3组成,在RNA代谢和蛋白质翻译中至关重要。但三者之间的功能并不完全相同,eIF4A1 主要通过 eIF4F 复合体促进 mRNA 翻译;eIF4A2 可促进特定促癌基因翻译,也参与 miRNA介导的翻译抑制;eIF4A3作为外显子连接复合体核心组分,调控RNA剪接等。在肿瘤治疗方面,抑制三者表达均展现出治疗潜力,但目前仍面临缺乏特异性抑制剂等问题。对 eIF4A家族的研究有助于深化对翻译调控网络的理解,为癌症治疗提供新策略。
关键词(KeyWords):
eIF4A;翻译调控;肿瘤治疗
参考文献(References):
[1]HUANG J, ZHANG L, YANG R, et al. Eukaryotic trans⁃ lation initiation factor 4A1 in the pathogenesis and treatment of cancers [J]. Front Mol Biosci,2023,10:1289650. [2]DU Y, XIE J, LIU D, et al. Critical and differential roles of eIF4A1 and eIF4A2 in B-cell development and function [J]. Cell Mol Immunol,2025,22(1):40-53.
[3]ZHU Y, REN C, YANG L. Effect of eukaryotic transla⁃ tion initiation factor 4A3 in malignant tumors (Review)[J]. Oncology Letters,2021,21(5):358-364.
[4]ZHAO Y, LI T, TIAN S, et al. Effective Inhibition of MYC-Amplified Group 3 Medulloblastoma Through Targeting EIF4A1[J]. Cancer Manag Res,2020,12:12473-12485. [5]WU C, LIU D, ZHANG L, et al. 5′-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I [J]. Frontiers of Medicine,2023,17(3):476-492.
[6]MA X, LI B, LIU J, et al. Phosphoglycerate dehydroge⁃ nase promotes pancreatic cancer development by interacting with eIF4A1 and eIF4E [J]. Journal of Experimental & Clinical Cancer Research,2019,38(1):66-80.
[7]LIU L, VUJOVIC A, DESHPANDE N P, et al. The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors [J]. Nature Communications,2022,13(1):3833-3849.
[8]MEIJER H A, SCHMIDT T, GILLEN S L, et al. DEADbox helicase eIF4A2 inhibits CNOT7 deadenylation activity [J]. Nucleic Acids Research,2019,47(15):8224-8238.
[9]MEIJER H A, KONG Y W, LU W T, et al. Translational Repression and eIF4A2 Activity Are Critical for MicroRNAMediated Gene Regulation [J]. Science,2013,340(6128): 82-85.
[10]LóPEZ ⁃ CáNOVAS J L, HERMáN ⁃ SáNCHEZ N, MORENO⁃MONTILLA M T, et al. Spliceosomal profiling identi⁃ fies EIF4A3 as a novel oncogene in hepatocellular carcinoma act⁃ ing through the modulation of FGFR4 splicing [J]. Clinical and Translational Medicine,2022,12(11): e1102.
[11]YANG X, TRIBOULET R, LIU Q, et al. Exon junction complex shapes the m6A epitranscriptome [J]. Nature Communi⁃ cations,2022,13(1):7904.
[12]JIANG X, GUO S, WANG S, et al. EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in DocetaxelResistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signal⁃ ing [J]. Cancer Research,2022,82(5):831-845.
[13]JINGUO XIA1, CHEN WU D S, YANHUI TANG,et al. CircMYH9 increases KPNA2 mRNA stability to promote hepa⁃ tocellular carcinoma progression in an EIF4A3-dependent manner [J]. American journal of cancer research,2022,12(9):4361- 4372.
[14]WANG X, LIU S, XU B, et al. circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Bind⁃ ing to eIF4A3[J]. Analytical Cellular Pathology,2021,2021: 1-11.
[15]ZHAO J, JIANG Y, CHEN L, et al. The EIF4A3/ CASC2/RORA Feedback Loop Regulates the Aggressive Pheno⁃ type in Glioblastomas [J]. Frontiers in Oncology,2021,11: 1-16. [16]RAMAN D, TIWARI A K. Role of eIF4A1 in triplenegative breast cancer stem-like cell-mediated drug resistance [J]. Cancer Rep (Hoboken),2022,5(12): e1299.
[17]CAO W, WEI W, ZHAN Z, et al. MiR-1284 modu⁃ lates multidrug resistance of gastric cancer cells by targeting EIF4A1[J]. Oncol Rep,2016,35(5):2583-2591.
[18]CHU J, GALICIA-VAZQUEZ G, CENCIC R, et al. CRISPR-Mediated Drug-Target Validation Reveals Selective Phar⁃ macological Inhibition of the RNA Helicase, eIF4A [J]. Cell Rep,2016,15(11):2340-2347.
[19]PETERS T L, TILLOTSON J, YEOMANS A M, et al. Target-Based Screening against eIF4A1 Reveals the Marine Natu⁃ ral Product Elatol as a Novel Inhibitor of Translation Initiation with In Vivo Antitumor Activity [J]. Clin Cancer Res,2018,24(17): 4256-4270.
[20]IWASAKI S, IWASAKI W, TAKAHASHI M, et al. The Translation Inhibitor Rocaglamide Targets a Bimolecular Cav⁃ ity between eIF4A and Polypurine RNA [J]. Mol Cell,2019,73 (4):738-748 e739.
[21]ESSEGIAN D J, CUNNINGHAM T A, ZERIO C J, et al. Molecular Dynamics Simulations Identify Tractable Lead-like Phenyl-Piperazine Scaffolds as eIF4A1 ATP-competitive Inhibi⁃ tors [J]. ACS Omega,2021,6(38):24432-24443.
[22]THOMPSON P A, EAM B, YOUNG N P, et al. Target⁃ ing Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A [J]. Molecular Cancer Therapeutics,2021,20(1):26-36.
[23]HOWARD C M, ESTRADA M, TERRERO D, et al. Identification of Cardiac Glycosides as Novel Inhibitors of eIF4A1- Mediated Translation in Triple-Negative Breast Cancer Cells [J]. Cancers (Basel),2020,12(8):2169-2186.
[24]STEINMANN S M, SANCHEZ-MARTIN A, TANZER E, et al. eIF4A1 Is a Prognostic Marker and Actionable Target in Human Hepatocellular Carcinoma [J]. Int J Mol Sci,2023,24 (3):2055-2073.
[25]CHEN Z-H, QI J-J, WU Q-N, et al. Eukaryotic initia⁃ tion factor 4A2 promotes experimental metastasis and oxaliplatin resistance in colorectal cancer [J]. Journal of Experimental & Clinical Cancer Research,2019,38(1):196-213.
[26]LIU M, GONG C, XU R, et al. MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2[J]. Cellular & Molecular Biology Letters,2019,24(1):1-11.
[27]YIN Y, XU W, SONG Y, et al. Icariin Regulates the hsa_circ_0003159/eIF4A3/bcl-2 Axis to Promote Gastric Cancer Cell Apoptosis [J]. Evidence-Based Complementary and Alterna⁃ tive Medicine,2022,2022:1-11.
[28]WEI Y, LU C, ZHOU P, et al. EIF4A3-induced circu⁃ lar RNA ASAP1 promotes tumorigenesis and temozolomide resis⁃ tance of glioblastoma via NRAS/MEK1/ERK1 – 2 signaling [J]. Neuro-Oncology,2021,23(4):611-624.
[29]WEI W, LIU K, HUANG X, et al. EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cis⁃ platin resistance [J]. Journal of Experimental & Clinical Cancer Research,2024,43(1):2-22.
[30]CHEN D, WANG Y, YANG F, et al. The circRAB3IP Mediated by eIF4A3 and LEF1 Contributes to Enzalutamide Resis⁃ tance in Prostate Cancer by Targeting miR-133a-3p/miR-133b/ SGK1 Pathway [J]. Frontiers in Oncology,2021,11:752573.
[31]ITO M, TANAKA T, CARY D R, et al. Discovery of Novel 1,4-Diacylpiperazines as Selective and Cell-Active eIF4A3 Inhibitors [J]. Journal of Medicinal Chemistry,2017,60(8): 3335-3351.
[32]MIZOJIRI R, NAKATA D, SATOH Y, et al. Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Deriva⁃ tives as Orally eIF4A3-Selective Inhibitors [J]. ACS Medicinal Chemistry Letters,2017,8(10):1077-1082.
[33]ITO M, IWATANI M, KAMADA Y, et al. Discovery of selective ATP-competitive eIF4A3 inhibitors [J]. Bioorganic & Medicinal Chemistry,2017,25(7):2200-2209.