Upregulation of MicroRNA-146a Increases the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy Through the Toll-Like Receptor-Signaling Pathway

被引:0
|
作者
Kandeel, Mahmoud [1 ,2 ]
Morsy, Mohamed Aly [3 ,4 ]
Abd El-Lateef, Hany Mohamed [5 ,6 ]
Marzok, Mohamed [7 ,8 ]
El-Beltagi, Hossam Saad [3 ,9 ,10 ]
Venugopala, Katharigatta Narayanaswamy [11 ]
机构
[1] King Faisal Univ, Dept Biomed Sci, Coll Vet Med, Al Hasa 31982, Saudi Arabia
[2] Kafrelsheikh Univ, Dept Pharmacol, Fac Vet Med, Kafr Al Sheikh 33516, Egypt
[3] King Faisal Univ, Dept Pharmaceut Sci, Coll Clin Pharm, Al Hasa 31982, Saudi Arabia
[4] Minia Univ, Dept Pharmacol, Fac Med, El Minia 61511, Egypt
[5] King Faisal Univ, Dept Chem, Coll Sci, Al Hasa 31982, Saudi Arabia
[6] Sohag Univ, Dept Chem, Fac Sci, Sohag 82524, Egypt
[7] King Faisal Univ, Dept Clin Sci, Coll Vet Med, Al Hasa 31982, Saudi Arabia
[8] Kafrelsheikh Univ, Dept Surg, Fac Vet Med, Kafr Al Sheikh 33516, Egypt
[9] King Faisal Univ, Dept Agr Biotechnol, Coll Agr & Food Sci, Al Hasa 31982, Saudi Arabia
[10] Cairo Univ, Dept Biochem, Fac Agr, Giza 12613, Egypt
[11] Durban Univ Technol, Fac Sci Appl, Dept Biotechnol & Food Sci, ZA-4000 Durban, South Africa
关键词
Cancer; microRNA; cisplatin; chemoresistance; gene expression; toll-like receptor; CYTOSCAPE;
D O I
10.3923/ijp.2023.749.757
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and Objective: Cisplatin, a platinum-based chemical, is a key agent in cancer treatment but is often associated with the development of resistance in several cancers. This resistance has been linked to miRNAs, which play crucial roles in gene regulation. In this study, the involvement of miRNAs in cisplatin resistance in NSCLC cells was explored. Materials and Methods: The differentially expressed miRNAs (DEMs) identified using the GSE43249 dataset and various bioinformatics tools. The experimental part involved culturing A549 cells, inducing cisplatin resistance, transfecting cells with miR-146a and assessing gene expression changes. Statistical analysis of the data was performed using R software and GraphPad Prism to elucidate the underlying mechanisms of drug resistance. Results: The downregulation of specific miRNAs, especially miR-146a. Functional studies revealed that miR-146a could target the TLR signaling pathway, a crucial pathway in cellular response. Notably, transfection with a miR-146a mimic increased the sensitivity of resistant cells to cisplatin, signifying a potential therapeutic avenue. Further, miR-146a was shown to downregulate the expression of key genes like TNF, MYD88 and IRAK1 in the resistant cells. Conclusion: This study provides insights into the molecular mechanisms behind cisplatin resistance in NSCLC cells and suggests potential therapeutic strategies leveraging miRNA modulation.
引用
收藏
页码:749 / 757
页数:9
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