The Role of DDX46 in the Occurrence And Development of Malignant Tumors
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摘要: 随着分子生物学的深入发展,人们对癌症发生机制的理解愈发深刻。近年来,大量研究发现DDX46在结直肠癌、食管鳞状细胞癌、胃癌等多种恶性肿瘤中过表达能促进多种恶性肿瘤细胞的增殖、侵袭和迁移,抵抗细胞凋亡,并参与细胞周期,因此可能成为潜在的抗肿瘤药物靶点和标志物。为了更直观地了解DDX46在癌症中的作用,系统地阐述其在肿瘤发生和发展的各个方面的功能及相关机制,为DDX46靶向药物的研发提供新思路。Abstract: With the deepening development of molecular biology, people's understanding of the mechanisms of cancer occurrence is becoming increasingly profound. In recent years, DDX46 has been found to be overexpressed in various cancers such as colorectal cancer, esophageal squamous cell carcinoma, and gastric cancer. It can promote the proliferation of various malignant tumor cells, activate invasion and migration, resist cell apoptosis, and participate in the cell cycle. Therefore, it may become a potential target and biomarker for anti-tumor drugs. To provide a more intuitive understanding of the role of DDX46 in cancer, we systematically describe its functions and related mechanisms in various aspects of tumorigenesis and development. It provides a new idea for the research and development of DDX46 targeted drugs.
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Key words:
- Molecular biology /
- DDX46 /
- Cancer /
- RNA helicase
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表 1 DDX46在多种肿瘤中的表达及临床特征
Table 1. Expression and clinical characteristics of DDX46 in various tumors
癌症类型 mRNA/蛋白质 高/低表达 百分比(%) 临床特征 胞质/核 参考文献 胶质母细胞瘤 mRNA and Protein 高 [18] 食管鳞状细胞癌 mRNA and Protein 高 32/69(46) 主要在胞核 [7] 低 30/69(43) 主要在胞核 乳腺癌 Protein 高 高级别组织学分级和淋巴结转移显著
相关,与更具有侵袭性的肿瘤表型相关主要在胞核 [20] 胃癌 mRNA 高 [5] 结直肠癌 Protein 高 99/123(81) 主要在胞核 [6] 低 19/123(15) 粘液腺癌比例高(8/11 73%) 主要在胞核 骨肉瘤 mRNA and Protein 高 [21] 皮肤鳞状细胞癌 mRNA and Protein 高 [19] 卵巢癌 Protein 高 [22] 慢性淋巴细胞白血病 高表达生存期短 [23] -
[1] Zhang Z M,Yang F,Zhang J. Crystal structure of Prp5p reveals interdomain interactions that impact spliceosome assembly[J]. Cell Rep,2013,5(5):1269-1278. doi: 10.1016/j.celrep.2013.10.047 [2] Will C L,Urlaub H,Achsel T. Characterization of novel SF3b and 17S U2 snRNP proteins,including a human Prp5p homologue and an SF3b DEAD-box protein[J]. EMBO,2002,21(18):4978-4988. doi: 10.1093/emboj/cdf480 [3] Zheng Q,Hou J,Zhou Y. The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus[J]. Nat Immunol,2017,18(10):1094-1103. [4] Yang F,Bian T,Zhan X. Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly[J]. Nat Commun,2023,14(1):897. doi: 10.1038/s41467-023-36489-x [5] Chen L,Xu M,Zhong W. Knockdown of DDX46 suppresses the proliferation and invasion of gastric cancer through inactivating Akt/GSK-3β/β-catenin pathway[J]. Exp Cell Res,2020,399(1):112448. [6] Li M,Ma Y,Huang P. Lentiviral DDX46 knockdown inhibits growth and induces apoptosis in human colorectal cancer cells[J]. Gene,2015,560(2):237-244. doi: 10.1016/j.gene.2015.02.020 [7] Li B,Li Y M,He W T. Knockdown of DDX46 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma cells[J]. Oncol Rep,2016,36(1):223-230. doi: 10.3892/or.2016.4803 [8] Bleichert F,Baserga S J. The long unwinding road of RNA helicases[J]. Mol Cell,2007,27(3):339-352. doi: 10.1016/j.molcel.2007.07.014 [9] Tanner N K, Linder P. DExD/H box RNA helicases: From generic motors to specific dissociation functions[J]. Mol Cell,2001,8(2):251-262. [10] Xu Y Z,Newnham C M,Kameoka S. Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA[J]. Embo J,2004,23(2):376-385. doi: 10.1038/sj.emboj.7600050 [11] Shao W. A U1-U2 snRNP interaction network during intron definition[J]. Mol Cell Biol,2012,32(2):470-478. doi: 10.1128/MCB.06234-11 [12] Will C L,Lührmann R. Spliceosome structure and function[J]. Cold Spring Harbor Perspect Biol,2011,3(7):a003707. [13] Liang W W,Cheng S C. A novel mechanism for Prp5 function in prespliceosome formation and proofreading the branch site sequence[J]. Genes Dev,2015,29(1):81-93. doi: 10.1101/gad.253708.114 [14] Gama-Brambila R A,Chen J,Zhou J. A PROTAC targets splicing factor 3B1[J]. Cell Chem Biol,2021,28(11):1616-1627. doi: 10.1016/j.chembiol.2021.04.018 [15] Yoshida K,Ogawa S. Splicing factor mutations and cancer[J]. Wires Rna,2014,5(4):445-459. doi: 10.1002/wrna.1222 [16] Xu Y Z,Query C C. Competition between the ATPase Prp5 and branch region-U2 snRNA pairing modulates the fidelity of spliceosome assembly[J]. Mol Cell,2007,28(5):838-849. doi: 10.1016/j.molcel.2007.09.022 [17] Abu Dayyeh B K,Quan T K,Castro M. Probing interactions between the U2 small nuclear ribonucleoprotein and the DEAD-box protein,Prp5[J]. J Biol Chem,2002,277(23):20221-20233. doi: 10.1074/jbc.M109553200 [18] Ma J,Gao Z,Liu X. DDX46 accelerates the proliferation of glioblastoma by activating the MAPK-p38 signaling[J]. J Buon,2021,26(5):2084-2089. [19] Lin Q,Jin H J. DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma[J]. Mol Med Rep,2020,22(5):4236-4242. [20] Ma Z,Song J. The role of DDX46 in breast cancer proliferation and invasiveness: A potential therapeutic target[J]. Cell Biol Int,2022,47(1):283-291. [21] Jiang,F,Zhang. Knockdown of DDX46 Inhibits the invasion and tumorigenesis in osteosarcoma cells[J]. Oncol Res,2016,25(3):417-425. [22] Asher V , Warren A , Shaw R. The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line[J]. Cancer Cell International,2011,11(1):1-7. [23] Admoni-Elisha L,Nakdimon I,Shteinfer A. Novel biomarker proteins in chronic lymphocytic leukemia: Impact on diagnosis,prognosis and treatment[J]. PLos One,2016,11(4):e0148500. doi: 10.1371/journal.pone.0148500 [24] Yang J, Nie J, Ma X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials[J]. Mol Cancer, 18(1): 26. [25] Faes S,Dormond O. PI3K and AKT: Unfaithful partners in cancer[J]. Int J Mol Sci,2015,16(9):21138-21152. doi: 10.3390/ijms160921138 [26] Peter M E. Programmed cell death: Apoptosis meets necrosis[J]. Nature,2011,471(7338):310-312. doi: 10.1038/471310a [27] Tanaka K, Kumano K, Ueno H. Intracellular signals of lung cancer cells as possible therapeutic targets[J]. Cancer Sci,2015,106(5):489-496. [28] You X,Cui H,Yu N. Knockdown of DDX46 inhibits trophoblast cell proliferation and migration through the PI3K/Akt/mTOR signaling pathway in preeclampsia[J]. Open Life Sci,2020,15(1):400-408. doi: 10.1515/biol-2020-0043 [29] Li A,He J,Zhang Z. Integrated bioinformatics analysis reveals marker genes and potential therapeutic targets for pulmonary arterial hypertension[J]. Genes (Basel),2021,12(9):1339. doi: 10.3390/genes12091339 [30] Hirabayashi,R,Hozumi. Ddx46 is required for multi-lineage differentiation of hematopoietic stem cells in zebrafish[J]. Stem Cells Dev,2013,22(18):2532-2542.