Open AccessExosomal circDNER enhances paclitaxel resistance and tumorigenicity of lung cancer via targeting miR ‐139‐5p/ ITGB8
Author(s) -
Li Jinyou,
Zhu Tao,
Weng Yuan,
Cheng Fengyue,
Sun Qi,
Yang Kejia,
Su Zhenyu,
Ma Haitao
Publication year - 2022
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.14402
Subject(s) - lung cancer , cancer research , downregulation and upregulation , microvesicles , paclitaxel , flow cytometry , microrna , medicine , western blot , cell growth , apoptosis , cancer , biology , immunology , oncology , biochemistry , gene
Background 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. Methods 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. Results 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. Conclusion 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.