Bioinformatics approach combined with experimental verification reveals OAS3 gene implicated in paclitaxel resistance in head and neck cancer

• Published in: Head & neck Vol. 46; no. 9; pp. 2178 - 2196
• Main Authors: Caglar, Hasan Onur, Aytatli, Abdulmelik, Barlak, Neslisah, Aydin Karatas, Elanur, Tatar, Arzu, Sahin, Abdulkadir, Karatas, Omer Faruk
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2024; Wiley Subscription Services, Inc
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Bioinformatics; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cell cycle; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Cell viability; Colonies; Computational Biology; DNA microarrays; Drug Resistance, Neoplasm - genetics; FaDu; Female; G1 phase; Gene expression; Gene Expression Regulation, Neoplastic; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; head and neck squamous cell carcinoma; Humans; Male; Middle Aged; OAS3; Paclitaxel; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; paclitaxel resistance; SCC‐9; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - pathology; Therapeutic targets; Tumor cell lines; SCC‐9; paclitaxel resistance; FaDu; OAS3; head and neck squamous cell carcinoma
• ISSN: 1043-3074; 1097-0347; 1097-0347
• DOI: 10.1002/hed.27803

Background This study aimed to identify a candidate gene associated with paclitaxel (PTX) resistance and to evaluate functionally its biological role in the PTX‐resistant head and neck squamous cell carcinoma (HNSCC) cell lines and clinical specimens. Methods Microarray data series containing samples of different types of cancers resistant to PTX were analyzed and then a candidate gene associated with PTX resistance was identified using various bioinformatics tools. After the suppression of the target gene expression, changes in cell viability and colony‐forming ability were evaluated in PTX‐resistant FaDu and SCC‐9 cell lines. Results Bioinformatics analyses of upregulated genes in PTX‐resistant cancer cells indicated that OAS3 was associated with PTX resistance. The downregulation of OAS3 expression significantly reduced the viability and colony‐forming capacity of PTX‐resistant SCC‐9 cells by inducing apoptosis and cell cycle arrest at G0/G1 phase. Conclusions The therapeutic targeting of OAS3 may resensitize PTX‐resistant HNSCC cells with high OAS3 expression to PTX treatment.