Exosomal transfer of miR-106a-5p contributes to cisplatin resistance and tumorigenesis in nasopharyngeal carcinoma.

Abstract

Nasopharyngeal carcinoma (NPC), a subclass of cancers of the neck and head, is a predominant cause of cancer-associated death worldwide. Hence, there is a critical need for research into NPC-related treatment strategies. Cisplatin is a promising therapy option for NPCs and other cancers that is frequently utilized. Some patients acquire resistance to cisplatin therapy, which complicates the successful use of cisplatin treatment in NPCs. Although exosomal transfer of oncogenic miRNAs has been shown to improve recipient cell proliferation, metastasis and chemoresistance, the molecular mechanism behind this effect on NPC has yet to be fully understood. Exosomal microRNAs (miRNAs) from cisplatin-resistant cells were identified as significant mediators of chemoresistance in NPC cells in this investigation. Initially, we found that exosomal miR-106a-5p levels in the serum of chemoresistant and last-cycle patients were greater than in that of non-resistant and first-cycle patients. Also, exosomal miR-106a-5p enhanced the proliferative ability of NPC cells. Mechanistically, exosomal miR-106a-5p targets ARNT2, which further activates AKT phosphorylation, and thus promotes NPC cell proliferation, decreases apoptosis and in turn regulates tumorigenesis. We found similar results using in vivo NPC models, where exosomal miR-106a-5p through regulation of ARNT2 (aryl hydrocarbon receptor nuclear translocator 2) promoted tumorigenesis. Taken together, these findings indicate that exosomal miR-106a-5p could be a promising diagnostic biomarker and drug target for patients with NPC.

• Authors: Jiaxing Li, Chaoquan Hu, Hui Chao, Yu Zhang, Yong Li, Jing Hou, Limin Huang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 19 Pg. 9183-9198 (10 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 34469038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• ARNT2 protein, human
• Basic Helix-Loop-Helix Transcription Factors
• MIRN106 microRNA, human
• MicroRNAs
• Aryl Hydrocarbon Receptor Nuclear Translocator
• Cisplatin

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Aryl Hydrocarbon Receptor Nuclear Translocator (genetics)
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Cisplatin (pharmacology)
• Databases, Genetic
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm (genetics)
• Exosomes (metabolism)
• Gene Expression Profiling
• Heterografts
• Humans
• Mice
• MicroRNAs (genetics, metabolism)
• Nasopharyngeal Carcinoma (genetics, metabolism)
• RNA Interference