PMID- 35339097
OWN - NLM
STAT- MEDLINE
DCOM- 20220519
LR  - 20220525
IS  - 1879-0534 (Electronic)
IS  - 0010-4825 (Linking)
VI  - 145
DP  - 2022 Jun
TI  - A computational study to assess the polymorphic landscape of matrix 
      metalloproteinase 3 promoter and its effects on transcriptional activity.
PG  - 105404
LID - S0010-4825(22)00196-2 [pii]
LID - 10.1016/j.compbiomed.2022.105404 [doi]
AB  - BACKGROUND: Matrix metalloproteinase 3 (MMP3) plays a crucial role in cancer 
      progression and development by proteolyzing extracellular matrix substrates. 
      Primarily, the expression of MMP3 is regulated at the transcriptional level. The 
      minute interplay of various transcription factor binding motifs at the promoter 
      region is responsible for the altered expression of the genes. Single nucleotide 
      polymorphism (SNP) at the transcription factor binding sites shows specific 
      effects on gene expressions. Genome-wide association study (GWAS) strongly 
      reported the association of common SNPs (rs3025058, rs522616, and rs617819) of 
      MMP3 promoter with disease progression. The insufficient functional analysis of 
      these promoter SNPs indicates the need for extensive mechanistic analysis on the 
      effects of allelic variants upon transcription factor binding at MMP3 promoter. 
      METHODS: The binding of transcription factors on the MMP3 promoter sequence was 
      investigated by a virtual laboratory. The interaction between the specific 
      transcription factor and promoter DNA with allelic variants was analyzed by 
      computational tools. RESULTS: It was found that transcription factor c-Myb and 
      Smad4 binding on MMP3 promoter were altered due to the presence of rs522616 and 
      rs617819 SNPs, respectively. Further, the binding affinity of Smad4 to the MMP3 
      promoter containing C allele at -375 region is higher than that of its allelic 
      variant G. CONCLUSION: This study presented that the complex of Smad4-DNA 
      fragment containing C allele has higher binding affinity and stability as 
      compared with its allelic variant. Hence, it is predicted that rs617819 
      polymorphism directly affects the Smad4 binding motif on MMP3 promoter and alters 
      its gene expression.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Banik, Payel
AU  - Banik P
AD  - School of Medical Science and Technology, Indian Institute of Technology, 
      Kharagpur, West Bengal, India; Department of Physiology, A.B.N. Seal College, 
      Cooch Behar, West Bengal, India.
FAU - Majumder, Ranabir
AU  - Majumder R
AD  - School of Medical Science and Technology, Indian Institute of Technology, 
      Kharagpur, West Bengal, India.
FAU - Mandal, Anik
AU  - Mandal A
AD  - Electronics and Electrical Communication Engineering, Indian Institute of 
      Technology, Kharagpur, West Bengal, India.
FAU - Dey, Sanjib
AU  - Dey S
AD  - Life Sciences Solutions Group, Thermo Fisher Scientific. Invitrogen Bioservices 
      India Pvt. Ltd, Kolkata, West Bengal, India.
FAU - Mandal, Mahitosh
AU  - Mandal M
AD  - School of Medical Science and Technology, Indian Institute of Technology, 
      Kharagpur, West Bengal, India. Electronic address: mahitosh@smst.iitkgp.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220315
PL  - United States
TA  - Comput Biol Med
JT  - Computers in biology and medicine
JID - 1250250
RN  - 0 (Transcription Factors)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - DNA
MH  - *Genome-Wide Association Study
MH  - *Matrix Metalloproteinase 3/genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Transcription Factors/genetics
OTO - NOTNLM
OT  - MMP3 promoter
OT  - Molecular docking
OT  - Molecular dynamics simulation
OT  - Polymorphism
OT  - SNP
OT  - Smad4
OT  - Transcription factor binding sites
OT  - rs617819
EDAT- 2022/03/27 06:00
MHDA- 2022/05/20 06:00
CRDT- 2022/03/26 20:12
PHST- 2021/11/30 00:00 [received]
PHST- 2022/03/11 00:00 [revised]
PHST- 2022/03/11 00:00 [accepted]
PHST- 2022/03/27 06:00 [pubmed]
PHST- 2022/05/20 06:00 [medline]
PHST- 2022/03/26 20:12 [entrez]
AID - S0010-4825(22)00196-2 [pii]
AID - 10.1016/j.compbiomed.2022.105404 [doi]
PST - ppublish
SO  - Comput Biol Med. 2022 Jun;145:105404. doi: 10.1016/j.compbiomed.2022.105404. Epub 
      2022 Mar 15.