DEAD-box RNA解旋酶3在肿瘤中作用机制的研究进展
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摘要
DEAD-box RNA解旋酶(DEAD-box helicase,DDX)在RNA代谢过程中发挥多种功能,对转录、剪切、mRNA转出、翻译、核糖体合成及miRNA的调控均有一定影响,其对RNA代谢的影响可引起一系列疾病的产生。DEAD-box RNA解旋酶3(DDX3)是DDX家族重要的成员,在细胞周期阻滞、细胞增殖和凋亡中起重要作用。DDX3可在多种肿瘤组织中发生异常表达,影响肿瘤患者的生存和预后。本文就DDX3在肿瘤,如肺癌、结直肠癌、乳腺癌及肝癌中作用机制的研究进展作一综述。
DEAD-box RNA helicase(DDX)plays several roles in RNA metabolism,which involves in the transcription,splicing,transfer of mRNA,translation,synthesis of ribosome and regulation of miRNA,resulting in the pathogenesis of a series of diseases. As a major member of DDX family,DDX3 plays an important role in the arrest of cell cycle as well as cell proliferation and apoptosis. DDX3 may be expressed abnormally in various tumor tissues,which affects the survival and causes unfavourable prognosis of patients with tumors. This paper reviews the action mechanisms of DDX3 in various tumors including lung cancer,colorectal cancer,breast cancer and liver cancer.
DEAD-box RNA helicase(DDX)plays several roles in RNA metabolism,which involves in the transcription,splicing,transfer of mRNA,translation,synthesis of ribosome and regulation of miRNA,resulting in the pathogenesis of a series of diseases. As a major member of DDX family,DDX3 plays an important role in the arrest of cell cycle as well as cell proliferation and apoptosis. DDX3 may be expressed abnormally in various tumor tissues,which affects the survival and causes unfavourable prognosis of patients with tumors. This paper reviews the action mechanisms of DDX3 in various tumors including lung cancer,colorectal cancer,breast cancer and liver cancer.
引文
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[25] BOTLAGUNTA M, KOLLAPALLI B, KAKARLA L, et al. In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3[J]. Bioinformation, 2016, 12(7):347-353.
[26] BOL G M, XIE M, RAMAN V. DDX3, a potential target for cancer treatment[J]. Mol Cancer,2015,14(1):88.
[27] MAJMUNDAR A J, WONG W J, SIMON M C. Hypoxia-inducible factors and the response to hypoxic stress[J]. Mol Cell,2010, 40(2):294-309.
[28] BOL G M, RAMAN V, VAN DER GROEP P, et al. Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer[J]. PLoS One, 2013, 8(5):e63548.
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[2] DINIS-OLIVEIRA R J, SOUSA C, REMIAO F, et al. Sodiun salicylate prevents paraquat-induced apoptosis in the rat lunp[J]. Free Radic Biol Med, 2007, 43(1):48-61.
[3] CHEN H H, YU H I, YANG M H, et al. DDX3 activates CBC-eIF3-mediated translation of uORF-containing oncogenic mRNAs to promote metastasis in HNSCC[J]. Cancer Res,2018,78(16):4512-4523.
[4] WANG Z, SHEN G H, XIE J M, et al. Rottlerin upregulates DDX3 expression in hepatocellular carcinoma[J]. Biochem Biophys Res Commun,2018,495(1):1503-1509.
[5] ARIUMI Y. Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection[J]. Frontiers in Genetics, 2014, 5(423):1-10.
[6] CHEN H H, YU H I, CHO W C, et al. DDX3 modulates cell adhesion and motility and cancer cell metastasis via Racl-mediated signaling pathway[J]. Oncogene, 2014, 34(21):2790-2800.
[7] FULLAM A, GU L, HOHN Y, et al. DDX3 directly facilitates IKKalpha activation and regulates downstream signalling pathways[J]. Biochem J, 2018, 475(22):3595-3607.
[8] HEERMA VAN VOSS M R, VESUNA F, BOL G M, et al.Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer[J]. Onco Targets Ther, 2017, 10(35):1-13.
[9] HATHAICHOTI S, VISITNONTHACHAI D, NGAMSIRI P, et al. Paraquat induces extrinsic pathway of apoptosis in A549cells by induction of DR5 and repression of anti-apoptotic proteins,DDX3 and GSK3 expression[J]. Toxicol In Vitro, 2017,42(12):3-9.
[10] TANTRAVEDI S, VESUNA F, WINNARD P T, et al. Targeting DDX3 in medulloblastoma using the small molecule inhibitor RK-33[J]. Translat Oncol, 2019, 12(1):96-105.
[11] ZHANG M, ATKINSON R L, ROSEN J M. Selective targeting of radiation-resistant tumor-initiating cells[J]. Proc Natl Acad Sci USA, 2010, 107(8):3522-3527.
[12] WU D W, LEE M C, WANG J, et al. DDX3 loss by p53 inactivation promotes tumor malignancy via the MDM2/Slug/Ecadherin pathway and poor patient outcome in non-small-cell lung cancer[J]. Oncogene, 2013, 33(12):1515-1526.
[13] LI J, MIZUKAMI Y, ZHANG X, et al. Oncogenic K-ras stimulates Wnt signaling in colon cancer through inhibition of GSK-3beta[J]. Gastroenterology, 2005, 128(7):1907-1918.
[14] SHAG D D, XUE W, KRALL E B, et al. KRAS and YAP1converge to regulate EMT and tumor survival[J]. Cell,2014,158(1):171-184.
[15] KARAPETIS C S, KHAMBATA-FORD S, JONKER D J, et al.K-ras mutations and benefit from cetuximab in advanced colorectal cancer[J]. N Engl J Med, 2008, 359(17):1757-1765.
[16] WU D W, LIN P L, WANG L, et al. The YAP1/SIX2 axis is required for DDX3-mediated tumor aggressiveness and cetuximab resistance in KRAS-wild-type colorectal cancer[J]. Theranostics, 2017, 7(5):1114-1132.
[17] HE T Y, WU D W, LIN P L, et al. DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis[J]. Sci Rep, 2016, 6(1):
[18] HEERMA VAN VOSS M R, VESUNA F, TRUMPI K, et al. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer[J]. Oncotarget, 2015,6(29):28312-28326.
[19] JANSSEN K P, ALBERICI P, FSIHI H, et al. APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal tumor formation and progression[J]. Gastroenterology,2006, 131(4):1096-1109.
[20] WU D W, LIN P L, CHENG Y W, et al. DDX3 enhances oncogenic KRAS induced tumor invasion in colorectal cancer via the betacatenin/ZEB1 axis[J]. Oncotarget, 2016, 7(16):22687-22699.
[21] SU C Y, LIN T C, LIN Y F, et al. DDX3 as a strongest prognosis marker and its dowregulation promotes metastasis in colorectal cancer[J]. Oncotarget, 2015, 6(21):18602-18612.
[22] FERLAY J, SHIN H R, BRAY F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J]. Int J Cancer, 2010, 127(12):2893-2917.
[23] SALIH A K, FENTIMAN I S. Breast cancer prevention:present and future[J]. Cancer Treat Rev, 2001, 27(5):261-273.
[24] HEERMA VAN VOSS M R, SCHRIJVER W A, TER HOEVE N D, et al. The prognostic effect of DDX3 upregulation in distant breast cancer metastases[J]. Clin Exp Metastasis, 2017,34(1):85-92.
[25] BOTLAGUNTA M, KOLLAPALLI B, KAKARLA L, et al. In vitro anti-cancer activity of doxorubicin against human RNA helicase, DDX3[J]. Bioinformation, 2016, 12(7):347-353.
[26] BOL G M, XIE M, RAMAN V. DDX3, a potential target for cancer treatment[J]. Mol Cancer,2015,14(1):88.
[27] MAJMUNDAR A J, WONG W J, SIMON M C. Hypoxia-inducible factors and the response to hypoxic stress[J]. Mol Cell,2010, 40(2):294-309.
[28] BOL G M, RAMAN V, VAN DER GROEP P, et al. Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer[J]. PLoS One, 2013, 8(5):e63548.
[29] XIE M, VESUNA F, BOTLAGUNTA M, et al.NZ51, a ringexpanded nucleoside analog, inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3[J].Oncotarget, 2015, 6(30):29901-29913.
[30] PATTABIRAMAN D R, WEINBERG R A. Tackling the cancer stem cells-what challenges do they pose[J]. Nat Rev Drug Discov, 2014, 13(7):497-512.
[31] LI H K, MAI R T, HUANG H D, et al. DDX3 represses stemness by epigenetically modulating tumor-suppressive miRNAs in hepatocellular carcinoma[J]. Sci Rep, 2016,6(1):1-19.