Document Type : Original Article(s)
Authors
- Amin Mehra 1
- Reza Mehrkar 2
- Amir Fakhri 3
- Pedram Jabbari Fard 4
- Mohammad Reza Asgharzadeh 3
- Mohammad Hossein Ghaffari Agdam 4
- Rasoul Sharifi 5
1 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Biology, Urmia Branch, Islamic Azad University, Urmia, Iran
4 Department of Microbiology, Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
5 Department of Biology, Ahar Branch, Islamic Azad University, Ahar, Iran
Abstract
Background: This study investigates the relative expression of the Na+, HCO3- cotransport gene NBCn1, and caspase-3 within the tumor microenvironment of human breast cancer, considering the in vivo microenvironment.
Method: In this experimental study, breast cancer MDA-MB-231 cells were cultured under normoxia/hypoxia conditions for 24, 48, and 72 hours with varying glucose concentrations (5.5, 11, and 25 mM). The mRNA expression of NBCn1 and caspase-3 was evaluated using real-time polymerase chain reaction. The stability and binding pocket of NBCn1 were assessed using DispHred and the Computed Atlas of Surface Topography of proteins (CASTp) servers, respectively. The location prediction of the protein was determined using the Transmembrane Helices; Hidden Markov Model (TMHMM) server.
Results: Normoxia led to an increase in NBCn1 expression during all three time periods, displaying heterogeneity. The expression was particularly elevated at glucose concentrations of 25 and 5.5 mM. In hypoxic conditions, gene expression was reduced; however, an increase in glucose concentration enhanced SLC4A7 expression. Specifically, a glucose concentration of 25 mM led to decreased caspase-3 expression under hypoxic conditions. In silico studies revealed that SLC4A7 becomes disordered when the pH falls below 7, with most amino acids in the binding pocket being nonpolar.
Conclusion: The heightened risk of breast cancer metastasis may be linked to the upregulation of SLC4A7 and downregulation of caspase-3 expression, underscoring their fundamental roles in cancer treatment and prevention. SLC4A7 is a transmembrane protein, and its folding is pH-dependent.
Highlights
Rasoul Sharifi (Google Scholar)
Keywords
Main Subjects
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2023.99391.1942
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