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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

TRIM45 Suppresses the Development of Non-small Cell Lung Cancer

Author(s): Xiyang Peng, Yao Wen, Lagabaiyila Zha, Jian Zhuang, Li Lin, Xu Li, Yu Chen, Zhiqiang Liu, Shuangli Zhu, Jifeng Liang, Zuoqiong Zhou, Wuzhou Yuan, Yongqing Li, Yuequn Wang, Zhigang Jiang, Xiaoyang Mo, Yongqi Wan, Yan Shi, Ping Zhu, Lan Zheng*, Changfa Tang*, Xiushan Wu* and Xiongwei Fan*

Volume 20, Issue 4, 2020

Page: [299 - 306] Pages: 8

DOI: 10.2174/1566524019666191017143833

Price: $65

Abstract

Background: Previously, we first identified the human tripartite motifcontaining protein 45 (TRIM45) acts as a novel transcriptional repressor in mitogenactivated protein kinase (MAPK) signaling pathway. After that, the inhibitory role of TRIM45 in the development of tumor was gradually unveiled. However, the function of TRIM45 in the tumorigenesis of lung cancer has not been characterized.

Methods and Results: In this study, we found that TRIM45 was up-regulated in earlystage human non-small-cell lung cancer (NSCLC) tissues. Overexpression of TRIM45 in lung cancer cells induces G1 arrest and promotes apoptosis, which accompanied by upregulated expression of RB, p16, p53, p27Kip1, and Caspase3 and down-regulated expression of CyclinE1 and CyclinE2. Further detection of the expression of the molecules in the MAPK signaling pathway revealed that overexpression of TRIM45 in lung cancer cells promotes phosphorylated p38 (p-p38) activation and inhibits phosphorylated ERK (p-ERK) activation. In accordance with this, p-p38 is increased while p-ERK is decreased in lung cancer tissues.

Conclusion: These findings indicate that TRIM45 plays an inhibitory role in the tumorigenesis of lung cancer. High-level expression of TRIM45 in lung cancer tissue may promote cell apoptosis by activating p38 signal and inhibit proliferation by down-regulating p-ERK, which provides a new clue for understanding the tumorigenesis of lung cancer.

Keywords: TRIM45, NSCLC, lung cancer, apoptosis, inhibitory role, MAPK pathway.

« Previous Next »
[1]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[2]
Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83(5): 584-94.
[http://dx.doi.org/10.1016/S0025-6196(11)60735-0] [PMID: 18452692]
[3]
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018; 553(7689): 446-54.
[http://dx.doi.org/10.1038/nature25183] [PMID: 29364287]
[4]
Reymond A, Meroni G, Fantozzi A, et al. The tripartite motif family identifies cell compartments. EMBO J 2001; 20(9): 2140-51.
[http://dx.doi.org/10.1093/emboj/20.9.2140] [PMID: 11331580]
[5]
Kano S, Miyajima N, Fukuda S, Hatakeyama S. Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2. Cancer Res 2008; 68(14): 5572-80.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6231] [PMID: 18632609]
[6]
Miyajima N, Maruyama S, Bohgaki M, et al. TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells. Cancer Res 2008; 68(9): 3486-94.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6059] [PMID: 18451177]
[7]
Quaderi NA, Schweiger S, Gaudenz K, et al. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet 1997; 17(3): 285-91.
[http://dx.doi.org/10.1038/ng1197-285] [PMID: 9354791]
[8]
Wang Y, Li Y, Qi X, et al. TRIM45, a novel human RBCC/TRIM protein, inhibits transcriptional activities of ElK-1 and AP-1. Biochem Biophys Res Commun 2004; 323(1): 9-16.
[http://dx.doi.org/10.1016/j.bbrc.2004.08.048] [PMID: 15351693]
[9]
Saurin AJ, Borden KL, Boddy MN, Freemont PS. Does this have a familiar RING? Trends Biochem Sci 1996; 21(6): 208-14.
[http://dx.doi.org/10.1016/S0968-0004(96)80017-X] [PMID: 8744354]
[10]
Zhang J, Zhang C, Cui J, et al. TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination. Cell Death Dis 2017; 8(5)e2831
[http://dx.doi.org/10.1038/cddis.2017.149] [PMID: 28542145]
[11]
Shibata M, Sato T, Nukiwa R, Ariga T, Hatakeyama S. TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation. Biochem Biophys Res Commun 2012; 423(1): 104-9.
[http://dx.doi.org/10.1016/j.bbrc.2012.05.090] [PMID: 22634006]
[12]
Lopez-Bergami P, Huang C, Goydos JS, et al. Rewired ERK-JNK signaling pathways in melanoma. Cancer Cell 2007; 11(5): 447-60.
[http://dx.doi.org/10.1016/j.ccr.2007.03.009] [PMID: 17482134]
[13]
Liu W, Yuan W, Li X, et al. ZNF424 Induces Apoptosis and Inhibits Proliferation in Lung Carcinoma Cells. Curr Mol Med 2018; 18(2): 109-15.
[http://dx.doi.org/10.2174/1566524018666180705113642] [PMID: 29974829]
[14]
Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270(5240): 1326-31.
[http://dx.doi.org/10.1126/science.270.5240.1326] [PMID: 7481820]
[15]
Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 2011; 75(1): 50-83.
[http://dx.doi.org/10.1128/MMBR.00031-10] [PMID: 21372320]
[16]
Tang C, Liang J, Qian J, et al. Opposing role of JNK-p38 kinase and ERK1/2 in hydrogen peroxide-induced oxidative damage of human trophoblast-like JEG-3 cells. Int J Clin Exp Pathol 2014; 7(3): 959-68.
[PMID: 24695490]
[17]
Maurer G, Tarkowski B, Baccarini M. Raf kinases in cancer-roles and therapeutic opportunities. Oncogene 2011; 30(32): 3477-88.
[http://dx.doi.org/10.1038/onc.2011.160] [PMID: 21577205]
[18]
Cao S, Zhu X, Du L. P38 MAP kinase is involved in oleuropein-induced apoptosis in A549 cells by a mitochondrial apoptotic cascade. Biomed Pharmacother 2017; 95: 1425-35.
[http://dx.doi.org/10.1016/j.biopha.2017.09.072]
[19]
Xu WT, Shen GN, Luo YH, et al. New naphthalene derivatives induce human lung cancer A549 cell apoptosis via ROS-mediated MAPKs, Akt, and STAT3 signaling pathways. Chem Biol Interact 2019; 304: 148.
[20]
Wang W, Wu J, Zhang Q, et al. Mitochondria-mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase. J Cell Biochem 2019; 120(4): 5480-94.
[http://dx.doi.org/10.1002/jcb.27827] [PMID: 30324629]
[21]
Yang X, Yao J, Luo Y, Han Y, Wang Z, Du L. P38 MAP kinase mediates apoptosis after genipin treatment in non-small-cell lung cancer H1299 cells via a mitochondrial apoptotic cascade. J Pharmacol Sci 2013; 121(4): 272-81.
[http://dx.doi.org/10.1254/jphs.12234FP] [PMID: 23603895]

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