LDB2 Inhibits Proliferation and Migration in Liver Cancer Cells by Abrogating Expression

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Dec 8

PMID 29212240

Citations 8

Authors

Hongyang Yu

Ruichun Jia

Ling Zhao

Shigang Song

Jing Gu

Haogang Zhang

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) was one of the most common cancers around the world, has very low 5-year survival rate. However, the mechanism of HCC occurrence and development is largely unknown. LDB2 belongs to the LIM-domain binding family and functions as an adaptor for transcriptional regulation. Here we found that LDB2 is downregulated in HCC samples. LDB2 has the ability to inhibit proliferation and migration of hepatocarcinoma cells. We found that the proliferation and migration abilities in HCC sample cells were impaired after LDB2 overexpression and vice versa. In mechanism, we found that LDB2 can recruit BRD7 to promoter and then block its expression. HEY1 whose expression is upregulated in HCC acts as an oncogene. In brief, our research reveals a new regulatory mechanism for hepatocarcinoma cell proliferation and migration.

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References

Yu X, Li Z, Shen J . BRD7: a novel tumor suppressor gene in different cancers. Am J Transl Res. 2016; 8(2):742-8. PMC: 4846923. View

Allemani C, Weir H, Carreira H, Harewood R, Spika D, Wang X . Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2014; 385(9972):977-1010. PMC: 4588097. DOI: 10.1016/S0140-6736(14)62038-9. View

Thaler J, Lee S, Jurata L, Gill G, Pfaff S . LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions. Cell. 2002; 110(2):237-49. DOI: 10.1016/s0092-8674(02)00823-1. View

Jia D, Wei L, Guo W, Zha R, Bao M, Chen Z . Genome-wide copy number analyses identified novel cancer genes in hepatocellular carcinoma. Hepatology. 2011; 54(4):1227-36. DOI: 10.1002/hep.24495. View

Sung W, Zheng H, Li S, Chen R, Liu X, Li Y . Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet. 2012; 44(7):765-9. DOI: 10.1038/ng.2295. View

Wu W, Hu K, Chen D, Zeng Z, Luo H, Wang F . Prognostic relevance of BRD7 expression in colorectal carcinoma. Eur J Clin Invest. 2012; 43(2):131-40. DOI: 10.1111/eci.12024. View

Roessler S, Jia H, Budhu A, Forgues M, Ye Q, Lee J . A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res. 2010; 70(24):10202-12. PMC: 3064515. DOI: 10.1158/0008-5472.CAN-10-2607. View

Choy L, Hagenbeek T, Solon M, French D, Finkle D, Shelton A . Constitutive NOTCH3 Signaling Promotes the Growth of Basal Breast Cancers. Cancer Res. 2017; 77(6):1439-1452. DOI: 10.1158/0008-5472.CAN-16-1022. View

Becker T, Ostendorff H, Bossenz M, Schluter A, Becker C, Peirano R . Multiple functions of LIM domain-binding CLIM/NLI/Ldb cofactors during zebrafish development. Mech Dev. 2002; 117(1-2):75-85. DOI: 10.1016/s0925-4773(02)00178-8. View

10.

Zheng Q, Zhao Y . The diverse biofunctions of LIM domain proteins: determined by subcellular localization and protein-protein interaction. Biol Cell. 2007; 99(9):489-502. DOI: 10.1042/BC20060126. View

11.

Chen Z, Huang L, Wu Y, Zhai W, Zhu P, Gao Y . LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression. Nat Commun. 2016; 7:12598. PMC: 4999516. DOI: 10.1038/ncomms12598. View

12.

Chen C, Wang Y, Pan Q, Tang Y, Wang Q, Pan K . Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma. Oncotarget. 2016; 7(13):16248-61. PMC: 4941311. DOI: 10.18632/oncotarget.7637. View

13.

Johnsen S, Gungor C, Prenzel T, Riethdorf S, Riethdorf L, Taniguchi-Ishigaki N . Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer. Cancer Res. 2009; 69(1):128-36. PMC: 2713826. DOI: 10.1158/0008-5472.CAN-08-1630. View

14.

Liu H, Zhou M, Luo X, Zhang L, Niu Z, Peng C . Transcriptional regulation of BRD7 expression by Sp1 and c-Myc. BMC Mol Biol. 2008; 9:111. PMC: 2632634. DOI: 10.1186/1471-2199-9-111. View

15.

Dawid I, Breen J, Toyama R . LIM domains: multiple roles as adapters and functional modifiers in protein interactions. Trends Genet. 1998; 14(4):156-62. DOI: 10.1016/s0168-9525(98)01424-3. View

16.

Agulnick A, Taira M, Breen J, Tanaka T, Dawid I, Westphal H . Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. Nature. 1996; 384(6606):270-2. DOI: 10.1038/384270a0. View

17.

Woltje K, Jabs M, Fischer A . Serum induces transcription of Hey1 and Hey2 genes by Alk1 but not Notch signaling in endothelial cells. PLoS One. 2015; 10(3):e0120547. PMC: 4370690. DOI: 10.1371/journal.pone.0120547. View

18.

Visvader J, Mao X, Fujiwara Y, Hahm K, Orkin S . The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc Natl Acad Sci U S A. 1998; 94(25):13707-12. PMC: 28370. DOI: 10.1073/pnas.94.25.13707. View

19.

Park Y, Lee J, Kim H, Lee Y, Kim T, Choi C . Tumor suppressive effects of bromodomain-containing protein 7 (BRD7) in epithelial ovarian carcinoma. Clin Cancer Res. 2013; 20(3):565-75. DOI: 10.1158/1078-0432.CCR-13-1271. View

20.

Li L, Jothi R, Cui K, Lee J, Cohen T, Gorivodsky M . Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells. Nat Immunol. 2010; 12(2):129-36. PMC: 3766981. DOI: 10.1038/ni.1978. View