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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

Regulation of TRIM24 by miR-511 modulates cell proliferation in gastric cancer

Authors: Ziling Fang, Ling Zhang, Quan Liao, Yi Wang, Feng Yu, Miao Feng, Xiaojun Xiang, Jianping Xiong

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

Background

Increasing evidence highlights the important roles of tripartite motif containing 24 (TRIM24) in tumor initiation and malignant progression in many tumors, including gastric cancer (GC). Although TRIM24 expression is remarkably upregulated during GC carcinogenesis, the molecular mechanisms underlying TRIM24 dysregulation remain unexplored.

Methods

In this study, miRNA target prediction tools were applied to explore miRNAs that potentially target TRIM24. Western blot and quantitative reverse-transcriptase PCR (qRT-PCR) were performed to detected TRIM24 and miR-511 expression in GC tissues and cell lines. Dual-luciferase reporter assay was utilized to validate if TRIM24 is a direct target gene of miR-511. CCK-8 assay, cell colony formation assay, EdU incorporation assay and cell cycle analysis were performed to determine whether miR-511-mediated regulation of TRIM24 could affect GC progression.

Results

In our study, miR-511 was found to be downregulated in GC and an inverse correlation was observed between TRIM24 and miR-511 expression in primary GC tissues and cell lines. Dual-luciferase reporter assay further verified TRIM24 is a direct target of miR-511. Functional assays showed miR-511 overexpression inhibited cell growth, colony formation ability and cell cycle progression. Conversely, inhibition of endogenous miR-511 promoted these phenotypes in GC cells. Moreover, reintroduction of TRIM24 rescued miR-511-induced inhibitory effects on GC cells. Furthermore, miR-511 elicits tumor-suppressive effects through inactivating PI3K/AKT and Wnt/β-catenin pathways by suppressing TRIM24.

Conclusions

Our results provide the new evidence supporting the tumor-suppressive role of miR-511 in GC by suppressing TRIM24, suggesting that this novel miR-511/TRIM24 axis is critical in the control of gastric cancer tumorigenesis.
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Literature
1.
2.
Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, et al. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol. 2013;14(12):e535–47.CrossRefPubMed
3.
Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, et al. TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010;468(7326):927–32.CrossRefPubMedPubMedCentral
4.
Chambon M, Orsetti B, Berthe ML, Bascoul-Mollevi C, Rodriguez C, Duong V, et al. Prognostic significance of TRIM24/TIF-1alpha gene expression in breast cancer. Am J Pathol. 2011;178(4):1461–9.CrossRefPubMedPubMedCentral
5.
Cui Z, Cao W, Li J, Song X, Mao L, Chen W. TRIM24 overexpression is common in locally advanced head and neck squamous cell carcinoma and correlates with aggressive malignant phenotypes. PLoS One. 2013;8(5):e63887.CrossRefPubMedPubMedCentral
6.
Liu X, Huang Y, Yang D, Li X, Liang J, Lin L, et al. Overexpression of TRIM24 is associated with the onset and progress of human hepatocellular carcinoma. PLoS One. 2014;9(1):e85462.CrossRefPubMedPubMedCentral
7.
Li H, Sun L, Tang Z, Fu L, Xu Y, Li Z, et al. Overexpression of TRIM24 correlates with tumor progression in non-small cell lung cancer. PLoS One. 2012;7(5):e37657.CrossRefPubMedPubMedCentral
8.
9.
Cambiaghi V, Giuliani V, Lombardi S, Marinelli C, Toffalorio F, Pelicci PG. TRIM proteins in cancer. Adv Exp Med Biol. 2012;770:77–91.CrossRefPubMed
10.
Thakkar KN, Stratton SA, Craig BM. Tissue-specific metabolism and TRIM24. Aging (Albany NY). 2015;7(10):736–7.CrossRef
11.
Pathiraja TN, Thakkar KN, Jiang S, Stratton S, Liu Z, Gagea M, et al. TRIM24 links glucose metabolism with transformation of human mammary epithelial cells. Oncogene. 2015;34(22):2836–45.CrossRefPubMed
12.
Li H, Wang Q, Bao H, Zhang H, Zhuang Y. Mechanism of TRIM24 to Regulate Resistance of Gefitinib in NSCLC cells. Zhongguo Fei Ai Za Zhi. 2016;19(1):24–9.PubMed
13.
Xue D, Zhang X, Zhang X, Liu J, Li N, Liu C, et al. Clinical significance and biological roles of TRIM24 in human bladder carcinoma. Tumour Biol. 2015;36(9):6849–55.CrossRefPubMed
14.
Zhang LH, Yin AA, Cheng JX, Huang HY, Li XM, Zhang YQ, et al. TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway. Oncogene. 2015;34(5):600–10.CrossRefPubMed
15.
Groner AC, Cato L, de Tribolet-Hardy J, Bernasocchi T, Janouskova H, Melchers D, et al. TRIM24 is an oncogenic transcriptional activator in prostate cancer. Cancer Cell. 2016;29(6):846–58.CrossRefPubMed
16.
Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, et al. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009;106(28):11612–6.CrossRefPubMedPubMedCentral
17.
18.
Jain AK, Allton K, Duncan AD, Barton MC. TRIM24 is a p53-induced E3-ubiquitin ligase that undergoes ATM-mediated phosphorylation and autodegradation during DNA damage. Mol Cell Biol. 2014;34(14):2695–709.CrossRefPubMedPubMedCentral
19.
Fang ZL, Deng J, Zhang L, Xiang XJ, Yu F, Chen J et al. TRIM24 promotes the aggression of gastric cancer via the Wnt/β-catenin signling pathway. Oncoloy lett. 2016. doi:10.​3892/​ol.​2017.​5604.
20.
Cheng Z, Wang HZ, Li X, Wu Z, Han Y, Li Y, et al. MicroRNA-184 inhibits cell proliferation and invasion, and specifically targets TNFAIP2 in Glioma. J Exp Clin Cancer Res. 2015;34:27.CrossRefPubMedPubMedCentral
21.
Xiang XJ, Deng J, Liu YW, Wan LY, Feng M, Chen J, et al. MiR-1271 inhibits cell proliferation, invasion and EMT in gastric cancer by targeting FOXQ1. Cell Physiol Biochem. 2015;36(4):1382–94.CrossRefPubMed
22.
Zhang J, Su B, Gong C, Xi Q, Chao T. miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade. Biochem Biophys Res Commun. 2016;478(1):337–42.CrossRefPubMed
23.
24.
25.
26.
Xie L, Qian X, Liu B. MicroRNAs: novel biomarkers for gastrointestinal carcinomas. Mol Cell Biochem. 2010;341(1–2):291–9.CrossRefPubMed
27.
Cao B, Wang K, Liao JM, Zhou X, Liao P, Zeng SX et al. Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation. Elife. 2016. 10.7554/eLife.15978.
28.
Han X, Fang Z, Wang H, Jiao R, Zhou J, Fang N. CUL4A functions as an oncogene in ovarian cancer and is directly regulated by miR-494. Biochem Biophys Res Commun. 2016. 10.1016/j.bbrc.2016.10.114.
29.
Xia JT, Chen LZ, Jian WH, Wang KB, Yang YZ, He WL, et al. MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-kappaB signaling. J Transl Med. 2014;12:33.CrossRefPubMedPubMedCentral
30.
Zhou X, Jin W, Jia H, Yan J, Zhang G. MiR-223 promotes the cisplatin resistance of human gastric cancer cells via regulating cell cycle by targeting FBXW7. J Exp Clin Cancer Res. 2015;34:28.CrossRefPubMedPubMedCentral
31.
Deng J, Lei W, Xiang XJ, Zhang L, Yu F, Chen J, et al. MicroRNA-506 inhibits gastric cancer proliferation and invasion by directly targeting Yap1. Tumour Biol. 2015;36(9):6823–31.CrossRefPubMed
32.
Liu J, Xue H, Zhang J, Suo T, Xiang Y, Zhang W, et al. MicroRNA-144 inhibits the metastasis of gastric cancer by targeting MET expression. J Exp Clin Cancer Res. 2015;34:35.CrossRefPubMedPubMedCentral
33.
Stone L. Prostate cancer: TRIM24 acts as a transcriptional activator. Nat Rev Urol. 2016;13(8):437.
34.
Ma L, Yuan L, An J, Barton MC, Zhang Q, Liu Z. Histone H3 lysine 23 acetylation is associated with oncogene TRIM24 expression and a poor prognosis in breast cancer. Tumour Biol. 2016;37(11):14803–12.CrossRefPubMed
35.
Zhang J, Chong CC, Chen GG, Lai PB. A seven-microRNA expression signature predicts survival in hepatocellular carcinoma. PLoS One. 2015;10(6):e0128628.CrossRefPubMedPubMedCentral
36.
Kim TH, Kim YK, Kwon Y, Heo JH, Kang H, Kim G, et al. Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours. Histopathology. 2010;57(5):734–43.CrossRefPubMed
37.
Zhang C, Chi YL, Wang PY, Wang YQ, Zhang YX, Deng J, et al. miR-511 and miR-1297 inhibit human lung adenocarcinoma cell proliferation by targeting oncogene TRIB2. PLoS One. 2012;7(10):e46090.CrossRefPubMedPubMedCentral
38.
Cao G, Dong W, Meng X, Liu H, Liao H, Liu S. MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3. Tumour Biol. 2015;36(6):4453–9.CrossRefPubMed
39.
Zhang HH, Pang M, Dong W, Xin JX, Li YJ, Zhang ZC, et al. miR-511 induces the apoptosis of radioresistant lung adenocarcinoma cells by triggering BAX. Oncol Rep. 2014;31(3):1473–9.PubMed
40.
Augello C, Gianelli U, Savi F, Moro A, Bonoldi E, Gambacorta M, et al. MicroRNA as potential biomarker in HCV-associated diffuse large B-cell lymphoma. J Clin Pathol. 2014;67(8):697–701.CrossRefPubMed
41.
Tserel L, Runnel T, Kisand K, Pihlap M, Bakhoff L, Kolde R, et al. MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4. J Biol Chem. 2011;286(30):26487–95.CrossRefPubMedPubMedCentral
42.
43.
Mayer IA, Arteaga CL. The PI3K/AKT pathway as a target for cancer treatment. Annu Rev Med. 2016;67:11–28.CrossRefPubMed
44.
Miao ZF, Wang ZN, Zhao TT, Xu YY, Wu JH, Liu XY, et al. TRIM24 is upregulated in human gastric cancer and promotes gastric cancer cell growth and chemoresistance. Virchows Arch. 2015;466(5):525–32.CrossRefPubMed
Metadata
Title
Regulation of TRIM24 by miR-511 modulates cell proliferation in gastric cancer
Authors
Ziling Fang
Ling Zhang
Quan Liao
Yi Wang
Feng Yu
Miao Feng
Xiaojun Xiang
Jianping Xiong
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-017-0489-1

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