Sudipta Deb Nath , Md Tamzid Hossain Tanim , Md. Mahmudul Hasan Akash , Mohammad Golam Mostafa , Abu Ashfaqur Sajib
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引用次数: 0
Abstract
Therapeutic resistance poses a significant challenge in treating most cancers and often leads to poor clinical outcomes and even treatment failure. One of the primary mechanisms that confer multidrug resistance phenotype to cancer cells is the hyperactivity of certain drug efflux transporters. P-GP, MRP1, and BCRP are the key ABC efflux pumps that collectively extrude a broad spectrum of chemotherapeutic drugs. Besides, HIF1A, a master transcription regulatory protein, is also associated with cancer development and therapeutic resistance. Thereby, this study aimed to delve into the mechanisms of drug resistance, specifically focusing on HIF1A-driven overexpression of ABC transporters. A total of 57 chemoresistant and 57 paired control tissue samples (breast, colorectal, and ovarian) from Bangladeshi cancer patients were analyzed to determine the co-expression level of ABC transporters and HIF1A. Molecular docking was also conducted to evaluate the interactions of HIF1A protein and hypoxia response element (HRE) sequences in the promoter regions transporter genes. This study revealed that HIF1A is significantly overexpressed in chemoresistant tissues, suggesting its pivotal role in chemoresistance mechanisms across malignancies and its potential as a target to overcome therapeutic resistance. The findings from this study also suggest a direct upregulation of ABCB1, ABCC1, and ABCG2 transcription by HIF1A in chemoresistant cancer cells by binding to the HRE sequence in the promoter regions. Thus, inhibition of these interactions of HIF1A appears to be a promising approach to reverse chemoresistance. The findings of this study can serve as a foundation for future research, resolving molecular intricacies to improve treatment outcomes in chemoresistant patients.
期刊介绍:
Journal of genetic engineering and biotechnology is devoted to rapid publication of full-length research papers that leads to significant contribution in advancing knowledge in genetic engineering and biotechnology and provide novel perspectives in this research area. JGEB includes all major themes related to genetic engineering and recombinant DNA. The area of interest of JGEB includes but not restricted to: •Plant genetics •Animal genetics •Bacterial enzymes •Agricultural Biotechnology, •Biochemistry, •Biophysics, •Bioinformatics, •Environmental Biotechnology, •Industrial Biotechnology, •Microbial biotechnology, •Medical Biotechnology, •Bioenergy, Biosafety, •Biosecurity, •Bioethics, •GMOS, •Genomic, •Proteomic JGEB accepts