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Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

Increased expression of MARCH8, an E3 ubiquitin ligase, is associated with growth of esophageal tumor

Authors: Shivam Singh, Anoop Saraya, Prasenjit Das, Rinu Sharma

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

Herein, for the first time, we report aberrant expression of membrane-associated RING-CH8 (MARCH8) in human esophageal squamous cell carcinoma. MARCH8 is a member of the recently discovered MARCH family of really interesting new genes (RING) E3 ligases. Though initial studies primarily focused on its immunomodulatory role, the newly discovered targets of this E3 ligase point towards its possible role in other biological processes such as embryogenesis and inhibition of apoptosis. However, its relevance in cancers is yet to be elucidated.

Methods

We carried out quantitative real time PCR and immunohistochemistry to examine the levels of MARCH8 mRNA and protein in esophageal squamous cell carcinoma tissues. The role of MARCH8 in esophageal cancer cells was evaluated by cell proliferation, clonogenic and migration/invasion assays and flow cytometry with MARCH8 gene knockdown.

Results

Significantly increased expression of MARCH8 mRNA was found in esophageal squamous cell carcinoma as compared to distant matched non-malignant tissues (p = 0.024, AUC = 0.654). Immunohistochemical analysis revealed overexpression of MARCH8 protein in 86% of esophageal squamous cell carcinoma tissues (p < 0.001, AUC = 0.908). Interestingly, intense nuclear staining of MARCH8 protein was detected in cancer cells in addition to its cytoplasmic expression. Knockdown of MARCH8 resulted in decreased proliferation, migration, invasion and clonogenic potential of esophageal cancer cells. In addition to this, silencing of MARCH8 induced apoptosis in esophageal cancer cells which was measured by cell cycle distribution assay which showed increase in sub G0 and G2/M populations (cell death) and decrease in S-phase population. To further check the type of apoptosis induced by MARCH8 silencing, annexin assay was performed which showed significant increase in the number of cells in early apoptotic phase.

Conclusions

Overall, increased expression of MARCH8 gene in preneoplastic and neoplastic esophageal tissues and its knockdown effect on cancer cell properties demonstrated herein points towards the potential role of this protein in esophageal tumorigenesis.
Literature
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefPubMed
2.
Coscoy L, Ganem D. PHD domains and E3 ubiquitin ligases: viruses make the connection. Trends Cell Biol. 2003;13:7–12.CrossRefPubMed
3.
Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP. Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002;416:703–9.CrossRefPubMed
4.
5.
Goto E, Ishido S, Sato Y, Ohgimoto S, Nagano-Fujii M, Hotta H. c-MIR, a human E3 ubiquitin ligase, is a functional homolog of herpesvirus proteins MIR1 and MIR2 and has similar activity. J Biol Chem. 2003;278:14657–68.CrossRefPubMed
6.
Ohmura-Hoshino M, Matsuki Y, Aoki M, Goto E, Mito M, Uematsu M, Kakiuchi T, Hotta H, Ishido S. Inhibition of MHC class II expression and immune responses by c-MIR. J Immunol. 2006;177:341–54.CrossRefPubMed
7.
8.
Bartee E, Mansouri M, Hovey Nerenberg B, Gouveia K, Früh K. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J Virol. 2004;78:1109–20.CrossRefPubMedPubMedCentral
9.
Eyster CA, Cole NB, Petersen S, Viswanathan K, Früh K, Donaldson JG. MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation. Mol Biol Cell. 2011;22:3218–30.CrossRefPubMedPubMedCentral
10.
Fujita H, Iwabu Y, Tokunaga K, Tanaka Y. Membrane-associated RING-CH (MARCH) 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor. J Cell Sci. 2013;126:2798–809.CrossRefPubMed
11.
Chen R, Li M, Zhang Y, Zhou Q, Shu HB. The E3 ubiquitin ligase MARCH8 negatively regulates IL-1β-induced NF-κB activation by targeting the IL1RAP coreceptor for ubiquitination and degradation. Proc Natl Acad Sci USA. 2012;109:14128–33.CrossRefPubMedPubMedCentral
12.
Van de Kooij B, Verbrugge I, de Vries E, Gijsen M, Montserrat V, Maas C, Neefjes J, Borst J. Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1. J Biol Chem. 2013;288:6617–28.CrossRefPubMedPubMedCentral
13.
14.
15.
Kumar A, Chatopadhyay T, Raziuddin M, Ralhan R. Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma using cDNA microarray. Int J Cancer. 2007;120:230–42.CrossRefPubMed
16.
Singh S, Saraya A, Sharma R. Increased levels of sperm protein 17 mRNA and circulating antibodies in periampullary carcinoma patients. Int J Clin Oncol. 2015;20:736–44.CrossRefPubMed
17.
Yu CS, Chen YC, Lu CH, Hwang JK. Prediction of protein subcellular localization. Proteins. 2006;64:643–51.CrossRefPubMed
18.
Kosugi S, Hasebe M, Tomita M, Yanagawa H. Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci USA. 2009;106:10171–6.CrossRefPubMedPubMedCentral
19.
Grosse-Wilde A, Voloshanenko O, Bailey SL, Longton GM, Schaefer U, Csernok AI, Schütz G, Greiner EF, Kemp CJ, Walczak H. TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development. J Clin Invest. 2008;118:100–10.CrossRefPubMed
20.
Vleminckx K, Vakaet L Jr, Mareel M, Fiers W, van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991;66:107–19.CrossRefPubMed
21.
22.
Shiozaki H, Oka H, Inoue M, Tamura S, Monden M. E-cadherin mediated adhesion system in cancer cells. Cancer. 1996;77:1605–13.CrossRefPubMed
23.
Toyomoto M, Ishido S, Miyasaka N, Sugimoto H, Kohsaka H. Anti-arthritic effect of E3 ubiquitin ligase, c-MIR, expression in the joints. Int Immunol. 2011;23:177–83.CrossRefPubMed
24.
Meng Y, Hu J, Chen Y, Yu T, Hu L. Silencing MARCH1 suppresses proliferation, migration and invasion of ovarian cancer SKOV3 cells via downregulation of NF-κB and Wnt/β-catenin pathways. Oncol Rep. 2016;36:2463–70.CrossRefPubMedPubMedCentral
25.
Hu J, Meng Y, Zhang Z, Yan Q, Jiang X, Lv Z, Hu L. MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells. Autophagy. 2017;13:333–44.CrossRefPubMed
Metadata
Title
Increased expression of MARCH8, an E3 ubiquitin ligase, is associated with growth of esophageal tumor
Authors
Shivam Singh
Anoop Saraya
Prasenjit Das
Rinu Sharma
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0490-y

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