Exosomal circDNER enhances paclitaxel resistance and tumorigenicity of lung cancer via targeting miR-139-5p/ITGB8.

Jinyou Li, Tao Zhu, Yuan Weng, Fengyue Cheng, Qi Sun, Kejia Yang, Zhenyu Su, Haitao Ma

Thoracic cancer 2022 May

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Circular RNAs (circRNAs) are regarded as vital regulatory factors in various cancers. However, the biological functions of circDNER in the paclitaxel (PTX) resistance of lung cancer remain largely unexplored. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze circDNER, miR-139-5p, and ITGB8. Cell proliferation was assessed via colony formation and MTT assays. Cell apoptosis was evaluated by flow cytometry. Western blot was performed to assess protein expression. The targeted interaction among circDNER, miR-139-5p, and ITGB8 were validated using dual-luciferase reporter or RNA immunoprecipitation assays. Inhibition of circDNER reduced IC50 of PTX, inhibited cell proliferation, invasion and migration, as well as promoted cell apoptosis in PTX-resistant lung cancer cells. Mechanistically, circDNER sponged miR-139-5p to upregulate ITGB8 expression. Overexpression of miR-139-5p reversed the biological functions mediated by circDNER in PTX-resistant lung cancer cells. MiR-139-5p overexpression suppressed PTX resistance and malignant behaviors of PTX-resistant lung cancer cells, with ITGB8 elevation rescued the impacts. Moreover, we demonstrated that circDNER was upregulated in plasma exosomes from lung cancer patients. The plasma exosomes derived from these patients are the key factors enhancing the migration and invasion potential of lung cancer cells. The circDNER mediated miR-139-5p/ITGB8 axis suppresses lung cancer progression. Our findings suggest that circDNER might act as a potential prognostic biomarker and therapeutic target for lung cancer treatment. © 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Citation

Jinyou Li, Tao Zhu, Yuan Weng, Fengyue Cheng, Qi Sun, Kejia Yang, Zhenyu Su, Haitao Ma. Exosomal circDNER enhances paclitaxel resistance and tumorigenicity of lung cancer via targeting miR-139-5p/ITGB8. Thoracic cancer. 2022 May;13(9):1381-1390