Oncotarget

Research Papers:

Differential expression of Mad2 gene is consequential to the patterns of histone H3 post-translational modifications in its promoter region in human esophageal cancer samples

Chongtham Sovachandra Singh, Nabamita Boruah, Atanu Banerjee, Sillarine Kurkalang, Pooja Swargiary, Hughbert Dakhar and Anupam Chatterjee _

Metrics: PDF 102 views  |   Full Text 884 views  |   ?  


Abstract

Chongtham Sovachandra Singh1,6, Nabamita Boruah2,6, Atanu Banerjee3,6, Sillarine Kurkalang4,6, Pooja Swargiary6, Hughbert Dakhar5 and Anupam Chatterjee1,6

1 School of Biosciences, The Assam Royal Global University, Guwahati, Assam 781035, India

2 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

3 Department of Zoology, LN Mithila University, Darbhanga, Bihar 846008, India

4 Comprehensive Cancer Center, University of Chicago Medicine, Chicago, IL 60637, USA

5 Histopathology Division, Nazareth Hospital, Laitumkhrah, Shillong 793003, India

6 Department of Biotechnology and Bioinformatics, Molecular Genetics Laboratory, North-Eastern Hill University, Shillong, Meghalaya 793022, India

Correspondence to:

Anupam Chatterjee, email: [email protected],
[email protected]

Keywords: Mad2 gene; histone methylation; histone acetylation; Rb-phosphorylation; esophageal cancer

Received: October 17, 2023     Accepted: December 28, 2023     Published: February 05, 2024

Copyright: © 2024 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Raw areca nut (AN) consumption increases esophageal squamous cell carcinoma (ESCC) due to overexpression of securin (pituitary tumor transforming gene1), causing chromosomal instability. Mitotic arrest deficient protein 2 (Mad2), a crucial spindle assembly checkpoint protein, is at risk of aneuploidy and tumor development when overexpressed or underexpressed. This study evaluates Mad2 status in human ESCC with AN consumption habits, revealing unclear molecular mechanisms. Human ESCC samples (n = 99) were used for loss of heterozygosity analysis at 4q25-28, while 32 samples were used for expression analysis of Mad2, E2F1 genes, and Rb-phosphorylation. Blood samples were used for metaphase preparation. The Mad2 deregulation was assessed using chromatin immunoprecipitation-qPCR assay in the core promoter region, establishing its association with the pRb-E2F1 circuit for the first time. The study revealed overexpression and underexpression of Mad2, premature anaphase, and chromosome missegregation in all the samples. LOH pattern identified a deletion in D4S2975 in 40% of ESCC samples. The study reveals the deregulation of pRb-E2F1 circuit in all samples. 4q27 disruption could be a factor for Mad2 underexpression in AN-induced esophageal carcinogenesis, while overexpression may be due to the deregulation of the Rb-E2F1 circuit and consequently elevation of H3K4me3 and H3K9ac. Mad2 expression levels with chromosomal abnormalities can be a clinical biomarker, but further research is needed to understand pRb’s role in Mad2 down-regulation.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 28554