Miz-1 promotes the proliferation of esophageal cancer cells via suppression of p21 and release of p21-arrested cyclin D1

Luo,Jun; Zhang,Cheng; Wang,Congyi; Li,Linjun; Li,Chunhong; Li,Qiang; Zhang,Min; Wu,Qingchen

doi:10.3892/or.2016.4731

Miz-1 promotes the proliferation of esophageal cancer cells via suppression of p21 and release of p21-arrested cyclin D1

Authors:
- Jun Luo
- Cheng Zhang
- Congyi Wang
- Linjun Li
- Chunhong Li
- Qiang Li
- Min Zhang
- Qingchen Wu
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Affiliations: Department of Cardiothoracic Surgery, The First Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing, P.R. China, Department of Cardiothoracic Surgery, People's Hospital of Changshou, Yuzhong, Chongqing, P.R. China, Department of Oncology, Suining Sichuan Center Hospital, Yuzhong, Sichuan, P.R. China
Published online on: April 4, 2016 https://doi.org/10.3892/or.2016.4731
Pages: 3532-3540

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Abstract

Tumorigenesis results from various types of dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation, apoptosis and senescence. The transcription factor Myc-interacting zinc finger protein 1 (Miz-1) can either activate or repress gene expression in concert with binding partners including the Myc oncoprotein in several types of tumors. Known target genes of these complexes encode the cyclin‑dependent kinase inhibitors such as cdkn2b (p15) and cdkn1a (p21). In the present study, we showed that the silencing of Miz-1 expression, through shRNA in a lentiviral vector, influenced various biological processes in two types of esophageal carcinoma cell lines. Silencing of the expression of Miz-1 inhibited cell proliferation and promoted apoptosis in vitro. Loss of Miz-1 reduced the migration ability in esophageal carcinoma cells. High expression of p21 and downregulation of cyclin D1 accompanied the knockdown of Miz-1. Our data demonstrated that esophageal cancer has a cell cycle arrest pathway via Miz-1, p21 and cyclin D1.

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1	Dang CV: c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol. 19:1–11. 1999. View Article : Google Scholar
2	Wu Y and Li Z: Oncogene c-myc and malignant tumor. Clin Res. 25:1698–1700. 2008.
3	Kotake T, Saiki S, Kinouchi T, Shiku H and Nakayama E: Detection of the c-myc gene product in urinary bladder cancer. Jpn J Cancer Res. 81:1198–1201. 1990. View Article : Google Scholar : PubMed/NCBI
4	Masters JR, Vesey SG, Munn CF, Evan GI and Watson JV: c-myc oncoprotein levels in bladder cancer. Urol Res. 16:341–344. 1988. View Article : Google Scholar : PubMed/NCBI
5	Levens D: Disentangling the MYC web. Proc Natl Acad Sci USA. 99:5757–5759. 2002. View Article : Google Scholar : PubMed/NCBI
6	Li LH, Nerlov C, Prendergast G, Macgregor D and Ziff EB: c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II. EMBO J. 13:4070–4079. 1994.PubMed/NCBI
7	Peukert K, Staller P, Schneider A, Carmichael G, Hänel F and Eilers M: An alternative pathway for gene regulation by Myc. EMBO J. 16:5672–5686. 1997. View Article : Google Scholar : PubMed/NCBI
8	Phan RT, Saito M, Basso K, Niu H and Dalla-Favera R: BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells. Nat Immunol. 6:1054–1060. 2005. View Article : Google Scholar : PubMed/NCBI
9	Basu S, Liu Q, Qiu Y and Dong F: gfi-1 represses CDKN2B encoding p15^INK4B through interaction with Miz-1. Proc Natl Acad Sci USA. 106:1433–1438. 2009. View Article : Google Scholar
10	Lu J, Chen M, Ren XR, Wang J, Lyerly HK, Barak L and Chen W: Regulation of Hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1. PLoS One. 8:e633532013. View Article : Google Scholar : PubMed/NCBI
11	Inoue S, Hao Z, Elia AJ, Cescon D, Zhou L, Silvester J, Snow B, Harris IS, Sasaki M, Li WY, et al: Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15. genes Dev. 27:1101–1114. 2013. View Article : Google Scholar : PubMed/NCBI
12	van Riggelen J, Müller J, Otto T, Beuger V, Yetil A, Choi PS, Kosan C, Möröy T, Felsher DW and Eilers M: The interaction between Myc and Miz1 is required to antagonize TGFbeta-dependent autocrine signaling during lymphoma formation and maintenance. genes Dev. 24:1281–1294. 2010. View Article : Google Scholar : PubMed/NCBI
13	Gebhardt A, Kosan C, Herkert B, Möröy T, Lutz W, Eilers M and Elsässer HP: Miz1 is required for hair follicle structure and hair morphogenesis. J Cell Sci. 120:2586–2593. 2007. View Article : Google Scholar : PubMed/NCBI
14	Seoane J, Le HV and Massagué J: Myc suppression of the p21^Cip1 Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature. 419:729–734. 2002. View Article : Google Scholar : PubMed/NCBI
15	Wu S, Cetinkaya C, Munoz-Alonso MJ, von der Lehr N, Bahram F, Beuger V, Eilers M, Leon J and Larsson LG: Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene. 22:351–360. 2003. View Article : Google Scholar : PubMed/NCBI
16	Adhikary S, Peukert K, Karsunky H, Beuger V, Lutz W, Elsässer HP, Möröy T and Eilers M: Miz1 is required for early embryonic development during gastrulation. Mol Cell Biol. 23:7648–7657. 2003. View Article : Google Scholar : PubMed/NCBI
17	Gebhardt A, Frye M, Herold S, Benitah SA, Braun K, Samans B, Watt FM, Elsässer HP and Eilers M: Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1. J Cell Biol. 172:139–149. 2006. View Article : Google Scholar : PubMed/NCBI
18	Saba I, Kosan C, Vassen L and Möröy T: IL-7R-dependent survival and differentiation of early T-lineage progenitors is regulated by the BTB/POZ domain transcription factor Miz-1. Blood. 117:3370–3381. 2011. View Article : Google Scholar : PubMed/NCBI
19	Hönnemann J, Sanz-Moreno A, Wolf E, Eilers M and Elsässer HP: Miz1 is a critical repressor of cdkn1a during skin tumorigenesis. PLoS One. 7:e348852012. View Article : Google Scholar : PubMed/NCBI
20	Liu J, Yan J, Jiang S, Wen J, Chen L, Zhao Y and Lin A: Site-specific ubiquitination is required for relieving the transcription factor Miz1-mediated suppression on TNF-α-induced JNK activation and inflammation. Proc Natl Acad Sci USA. 109:191–196. 2012. View Article : Google Scholar
21	Li Z and Li B: Correlation of gene polymorphism of p21 and p27 with tumor. Int J gene. 29:317–320. 2006.
22	Krauss Gerhard; Sun C, Liu JS, et al: Biochemistry of Signal Transduction and Regulation. Chemical Industry Press; pp. 338–377. 2005
23	Palazzo JP, Mercer WE, Kovatich AJ and McHugh M: Immunohistochemical localization of p21^WAF1/CIP1 in normal, hyperplastic, and neoplastic uterine tissues. Hum Pathol. 28:60–66. 1997. View Article : Google Scholar : PubMed/NCBI
24	Zhang J, Lv H, Jing L and Qin J: Expression of p21^cip1/WAF, p53 and the infection of HPV-16 in the esophageal cancer. Shi Yong Ai Zheng Za Zhi She. 19:488–490. 2004.In Chinese.
25	Tanaka Y, Fujii T, Yamana H, Kato S, Morimatsu M and Shirouzu K: Experimental gene therapy using p21^Waf1 gene for esophageal squamous cell carcinoma by gene gun technology. Int J Mol Med. 14:545–551. 2004.PubMed/NCBI
26	Liu J, Hu Y, Hu W, Xie X, Ela Bella A, Fu J and Rao D: Expression and prognostic relevance of p21^WAF1 in stage III esophageal squamous cell carcinoma. Dis Esophagus. 25:67–71. 2012. View Article : Google Scholar
27	Zhang H, Liu Y and Hu M: Expression and significance of p53, p21, p16, cyclin D and CDK, in esophageal squamous cell carcinoma. Immunological J. 4:312–315. 2003.
28	Möröy T, Saba I and Kosan C: The role of the transcription factor Miz-1 in lymphocyte development and lymphomagenesis-binding Myc makes the difference. Semin Immunol. 23:379–387. 2011. View Article : Google Scholar : PubMed/NCBI
29	Montgomery EA: Oesophageal cancer. (World Cancer Report 2014). Stewart BW and Wild CP: International Agency for Research on Cancer; Lyon: pp. 374–382. 2014
30	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Gobal cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
31	Chen W, Zheng R, Zhang S, Zhao P, Zeng H and Zou X: Report of cancer incidence and mortality in China, 2010. Ann Transl Med. 2:612014.PubMed/NCBI
32	Deshpande A, Sicinski P and Hinds PW: Cyclins and cdks in development and cancer: A perspective. Oncogene. 24:2909–2915. 2005. View Article : Google Scholar : PubMed/NCBI