FoxO6 inhibits cell proliferation in lung carcinoma through up-regulation of USP7

Hu,Hong-Jun; Zhang,Li-Guo; Wang,Zhen-Hua; Guo,Xi-Xi

doi:10.3892/mmr.2015.3362

FoxO6 inhibits cell proliferation in lung carcinoma through up-regulation of USP7

Authors:
- Hong-Jun Hu
- Li-Guo Zhang
- Zhen-Hua Wang
- Xi-Xi Guo
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Affiliations: Department of Thoracic Tumor Surgery 2, Xinxiang Central Hospital, Xinxiang, Henan 453000, P.R. China
Published online on: February 17, 2015 https://doi.org/10.3892/mmr.2015.3362
Pages: 575-580

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Abstract

Emerging evidence has suggested that misregulation of oncogenes and/or tumor suppressors has a crucial role in the development of lung carcinoma. The present study demonstrated that the expression levels of forkhead box O6 (FOXO6) were downregulated in lung cancer tissue samples, as compared with those in adjacent normal tissue. Overexpression of FOXO6 inhibited the proliferation of A549 human lung cancer cells, whereas knockdown of endogenous FOXO6 expression enhanced cell proliferation. Furthermore, ectopic FOXO6 expression induced the expression of ubiquitin‑specific‑processing protease 7 (USP7). As a result of this regulation, FOXO6 overexpression led to an elevation of p53 protein expression levels in A549 cells. In conclusion, the results of the present study indicated that the FOXO6/USP7 molecular network has an important role in the regulation of lung cancer development.

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1	Hutchinson L: Screening: Improved model for lung cancer detection. Nat Rev Clin Oncol. 10:1832013. View Article : Google Scholar : PubMed/NCBI
2	Keith RL and Miller YE: Lung cancer chemoprevention: current status and future prospects. Nat Rev Clin Oncol. 10:334–343. 2013. View Article : Google Scholar : PubMed/NCBI
3	Mallakin A, Sugiyama T, Taneja P, et al: Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer. Cancer Cell. 12:381–394. 2007. View Article : Google Scholar : PubMed/NCBI
4	Damsky WE, Curley DP, Santhanakrishnan M, et al: β-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. Cancer Cell. 20:741–754. 2011. View Article : Google Scholar : PubMed/NCBI
5	Eijkelenboom A and Burgering BM: FOXOs: signalling integrators for homeostasis maintenance. Nat Rev Mol Cell Biol. 14:83–97. 2013. View Article : Google Scholar : PubMed/NCBI
6	Lam EW, Brosens JJ, Gomes AR and Koo CY: Forkhead box proteins: tuning forks for transcriptional harmony. Nat Rev Cancer. 13:482–495. 2013. View Article : Google Scholar : PubMed/NCBI
7	Santo EE, Stroeken P, Sluis PV, Koster J, Versteeg R and Westerhout EM: FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma. Cancer Res. 73:2189–2198. 2013. View Article : Google Scholar : PubMed/NCBI
8	Savkovic SD: Decreased FOXO3 within advanced human colon cancer: implications of tumour suppressor function. Br J Cancer. 109:297–298. 2013. View Article : Google Scholar : PubMed/NCBI
9	Hong ZY, Lee HJ, Shin DY, Kim SK, Seo M and Lee EJ: Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines. Cancer Lett. 314:34–40. 2012. View Article : Google Scholar
10	Salih DA, Rashid AJ, Colas D, et al: FoxO6 regulates memory consolidation and synaptic function. Genes Dev. 26:2780–2801. 2012. View Article : Google Scholar : PubMed/NCBI
11	Kim DH, Perdomo G, Zhang T, et al: FoxO6 integrates insulin signaling with gluconeogenesis in the liver. Diabetes. 60:2763–2774. 2011. View Article : Google Scholar : PubMed/NCBI
12	Kim DH, Zhang T, Lee S, et al: FoxO6 integrates insulin signaling with MTP for regulating VLDL production in the liver. Endocrinology. 155:1255–1267. 2014. View Article : Google Scholar : PubMed/NCBI
13	Li M, Chen D, Shiloh A, et al: Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 416:648–653. 2002. View Article : Google Scholar : PubMed/NCBI
14	Hopewell EL, Zhao W, Fulp WJ, et al: Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. J Clin Invest. 123:2509–2522. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhang G, Li J, Purkayastha S, et al: Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature. 497:211–216. 2013. View Article : Google Scholar : PubMed/NCBI
16	Saha A, Kuzuhara T, Echigo N, Fujii A, Suganuma M and Fujiki H: Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of “growth arrest and DNA damage inducible genes 45 and 153”. Biol Pharm Bull. 33:1291–1299. 2010. View Article : Google Scholar
17	Dar A, Shibata E and Dutta A: Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway. Mol Cell Biol. 33:3309–3320. 2013. View Article : Google Scholar : PubMed/NCBI
18	de Rozieres S, Maya R, Oren M and Lozano G: The loss of mdm2 induces p53-mediated apoptosis. Oncogene. 19:1691–1697. 2000. View Article : Google Scholar : PubMed/NCBI
19	Sui G, Affar el B, Shi Y, et al: Yin Yang 1 is a negative regulator of p53. Cell. 117:859–872. 2004. View Article : Google Scholar : PubMed/NCBI
20	Holowaty MN, Zeghouf M, Wu H, et al: Protein profiling with Epstein-Barr nuclear antigen-1 reveals an interaction with the herpesvirus-associated ubiquitin-specific protease HAUSP/USP7. J Biol Chem. 278:29987–29994. 2003. View Article : Google Scholar : PubMed/NCBI
21	Li M, Brooks CL, Kon N and Gu W: A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell. 13:879–886. 2004. View Article : Google Scholar : PubMed/NCBI
22	Fang S, Jensen JP, Ludwig RL, Vousden KH and Weissman AM: Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 275:8945–8951. 2000. View Article : Google Scholar : PubMed/NCBI
23	Iwakuma T and Lozano G: MDM2, an introduction. Mol Cancer Res. 1:993–1000. 2003.
24	Jung CH, Kim J, Park JK, et al: Mdm2 increases cellular invasiveness by binding to and stabilizing the Slug mRNA. Cancer Lett. 335:270–277. 2013. View Article : Google Scholar : PubMed/NCBI
25	Qinyu L, Long C, Zhen-dong D, et al: FOXO6 promotes gastric cancer cell tumorigenicity via upregulation of C-myc. FEBS Lett. 587:2105–2111. 2013. View Article : Google Scholar : PubMed/NCBI