MicroRNA-101-3p inhibits nasopharyngeal carcinoma cell proliferation and cisplatin resistance through ZIC5 down-regulation by targeting SOX2.

Abstract

This study aims to explore the mechanism of microRNA (miR)-101-3p-mediated SOX2/ZIC5 axis in the progression of cisplatin resistance of nasopharyngeal carcinoma (NPC). ZIC5 expression was analyzed with a bioinformatics database and detected in NPC cell lines. Cisplatin-resistant cells (HNE-1/DDP and C666-1/DDP) were transfected with sh-ZIC5, sh-SOX2, sh-SOX2 + pcDNA3.1-ZIC5, or miR-101-3p Agomir + pcDNA3.1-SOX2. MiR-101-3p, SOX2, and ZIC5 expression was assessed after transfection, and cancer associated phenotypes were evaluated after cisplatin treatment. The potential relationships among miR-101-3p, SOX2, and ZIC5 were analyzed. A xenograft mouse model of NPC was established with HNE-1 cells stably transfected or not transfected with oe-ZIC5 and subjected to tail vein injection of miR-101-3p Agomir and intraperitoneal injection of cisplatin. Overexpression of ZIC5 was found in cisplatin-resistant NPC cells. Downregulating ZIC5 in NPC cells decreased cell viability, promoted apoptosis, and reduced cisplatin resistance. SOX2 had a binding site on ZIC5, and SOX2 promoted proliferation, migration, and cisplatin resistance and inhibited cell apoptosis by up-regulating ZIC5. Mechanistically, miR-101-3p was decreased in cisplatin-resistant NPC cells and negatively targeted SOX2. Overexpression of miR-101-3p inhibited tumor growth and cisplatin resistance in xenograft mouse model, which was reversed by ZIC5 overexpression. In conclusion, the miR-101-3p/SOX2/ZIC5 axis was implicated in cancer associated phenotypes and cisplatin resistance in NPC.

• Authors: Tieqi Li, Gehou Zhang, Wei Li, Jian Xiao, Zheng Zhou, Guolin Tan, Jingang Ai
• Journal: Biological chemistry (Biol Chem) Vol. 404 Issue 10 Pg. 961-975 (09 26 2023) ISSN: 1437-4315 [Electronic] Germany
• PMID: 36752150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Walter de Gruyter GmbH, Berlin/Boston.

Chemical References

• MicroRNAs
• Cisplatin
• ZIC5 protein, human
• DNA-Binding Proteins
• Transcription Factors
• SOX2 protein, human
• SOXB1 Transcription Factors
• MIRN101 microRNA, human
• MIRN101 microRNA, mouse

Topics

• Humans
• Animals
• Mice
• Nasopharyngeal Carcinoma (drug therapy, genetics)
• MicroRNAs (genetics, metabolism)
• Cisplatin (pharmacology)
• Down-Regulation
• Cell Line, Tumor
• Nasopharyngeal Neoplasms (drug therapy, genetics, pathology)
• Cell Proliferation
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic
• DNA-Binding Proteins (metabolism)
• Transcription Factors (metabolism)
• SOXB1 Transcription Factors (genetics, metabolism)