• Users Online: 592
  • Print this page
  • Email this page
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 1  |  Page : 25-33

Transforming growth factor beta receptor 2 single-nucleotide polymorphism association with oral cancer and In silico identification of small drug-like molecules as inhibitors to transforming growth factor Beta-2 receptor


1 Department of Biological Sciences, Sunandan Divatia School of Science, SVKM's NMIMS (Deemed-to-be) University, Mumbai, Maharashtra, India
2 Dr. Kantilal J. Sheth Memorial Building, 84-A, RG Thadani Marg, Worli, Mumbai, Maharashtra, India

Correspondence Address:
Dr. Dhananjaya Saranath
Dr. Kantilal J. Sheth Memorial Building, 84-A, RG Thadani Marg, Worli, Mumbai - 400 018, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/BMRJ.BMRJ_1_19

Rights and Permissions

Objective: Oral cancer, in India, constitutes 26% of global oral cancer burden. The major risk factors include tobacco, areca nut, alcohol, and human papillomavirus 16/18; however, only 5%–10% of the high-risk individuals develop oral cancer, indicating the role of genomic variants in susceptibility to oral cancer. Conventional treatment options in oral cancer have resulted in relatively poor prognosis and an unmet need of treatment. In silico analysis, therefore, was performed to identify small drug-like molecules as potential inhibitors of transforming growth factor beta-2 receptor (TGFβRII). Materials and Methods: Seven single-nucleotide polymorphisms (SNPs) were analyzed in 500 histopathologically confirmed oral cancer samples and 500 long-term tobacco users (LTTUs) as controls using allelic discrimination real-time polymerase chain reaction or high-resolution melting analysis. The differential frequencies in oral cancer and LTTUs were calculated using SPSS software (version 19), and odds ratio (OR) to indicate risk to oral cancer using Hutchon.net. structure-based virtual screening of drug-like molecules was performed to identify lead inhibitor molecules to TGFβRII using Schrödinger Suite 2015-4. Results: Heterozygous GC genotype of TGFBR2 rs9843143 demonstrated increased risk ([P = 0.011; OR 1.61 [1.25–2.1]) while CC genotype showed decreased risk (P = 0.005; OR 0.61 [0.44–0.83]) to oral cancer. Increased/decreased risk to oral cancer was not observed for the other SNPs. In silico analysis identified six molecules as inhibitors of TGFβRII kinase domain from 17,723 conformers from Maybridge HitFinder library and 2685 conformers from MEGx AnalytiCon natural product library. Conclusion: SNP rs9843143 (TGFBR2) demonstrated a significant association (P < 0.05) with oral cancer and six potential inhibitors of TGFβRII kinase were identified using in silico analysis.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed5078    
    Printed397    
    Emailed0    
    PDF Downloaded410    
    Comments [Add]    
    Cited by others 1    

Recommend this journal