A Mimicry of the Tumor Microenvironment's Impact on SLC4A7 (NBCn1) and Caspase-3 Gene Expression in Breast Cancer, along with in Silico Traits of NBCn1 | ||
| Middle East Journal of Cancer | ||
| مقاله 2، دوره 15، شماره 3 - شماره پیاپی 59، پاییز 2024، صفحه 176-188 اصل مقاله (5.85 M) | ||
| نوع مقاله: Original Article(s) | ||
| شناسه دیجیتال (DOI): 10.30476/mejc.2023.99391.1942 | ||
| نویسندگان | ||
| Amin Mehra1؛ Reza Mehrkar2؛ Amir Fakhri3؛ Pedram Jabbari Fard4؛ Mohammad Reza Asgharzadeh3؛ Mohammad Hossein Ghaffari Agdam4؛ Rasoul Sharifi* 5، 6 | ||
| 1Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 2Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 3Department of Biology, Urmia Branch, Islamic Azad University, Urmia, Iran | ||
| 4Department of Microbiology, Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran | ||
| 5Department of Biology, Ahar Branch, Islamic Azad University, Ahar, Iran | ||
| 6Department of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran | ||
| چکیده | ||
| 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. | ||
تازه های تحقیق | ||
Rasoul Sharifi (Google Scholar) | ||
| کلیدواژهها | ||
| Tumor microenvironment؛ SLC4A7؛ Caspase-3؛ Breast neoplasms؛ In silico | ||
| مراجع | ||
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