Chunhong Guo1, Hailiang Wang1, Housen Jiang2, Liang Qiao3, Xinli Wang1. 1. Department of Pharmacy Intravenous Admixture Service, Weifang People's Hospital, Weifang, China. 2. Department of Orthopedic Surgery, Weifang People's Hospital, Weifang, China. 3. Department of Urology, Gaomi People's Hospital, Gaomi, China.
Abstract
Background: Non-small cell lung cancer (NSCLC) is the most prevalent cancer in the world. Chemotherapy resistance is a major obstacle to NSCLC therapy. This study explored the role and molecular mechanism of circular RNA 0011292 (circ_0011292) in tumorigenesis and chemoresistance of NSCLC. Methods: The levels of circ_0011292, miR-379-5p, and tripartite motif-containing protein 65 (TRIM65) were measured by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was monitored by flow cytometry. Cell migration and invasion were detected by transwell assay. The levels of apoptosis-related and epithelial-mesenchymal transition-related proteins were examined by Western blot. The half-inhibition concentration (IC50) of paclitaxel (PTX) was evaluated by CCK-8 assay. Xenograft model was established to analyze the effect of circ_0011292 on PTX resistance of NSCLC in vivo. The interaction among circ_0011292, miR-379-5p, and TRIM65 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0011292 and TRIM65 were upregulated, while miR-379-5p was downregulated in NSCLC tissues and cells. Circ_0011292 knockdown hindered NSCLC progression and enhanced PTX sensitivity of NSCLC. Circ_0011292 silencing reduced PTX resistance in vivo. Besides, miR-379-5p potentiated PTX sensitivity by targeting TRIM65. Also, circ_0011292 increased PTX resistance by sponging miR-379-5p. Conclusion: Circ_0011292 facilitated tumorigenesis and PTX resistance in NSCLC by regulating the miR-379-5p/TRIM65 axis, suggesting that circ_0011292 was a promising therapeutic target for NSCLC chemotherapy.
Background: Non-small cell lung cancer (NSCLC) is the most prevalent cancer in the world. Chemotherapy resistance is a major obstacle to NSCLC therapy. This study explored the role and molecular mechanism of circular RNA 0011292 (circ_0011292) in tumorigenesis and chemoresistance of NSCLC. Methods: The levels of circ_0011292, miR-379-5p, and tripartite motif-containing protein 65 (TRIM65) were measured by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was monitored by flow cytometry. Cell migration and invasion were detected by transwell assay. The levels of apoptosis-related and epithelial-mesenchymal transition-related proteins were examined by Western blot. The half-inhibition concentration (IC50) of paclitaxel (PTX) was evaluated by CCK-8 assay. Xenograft model was established to analyze the effect of circ_0011292 on PTX resistance of NSCLC in vivo. The interaction among circ_0011292, miR-379-5p, and TRIM65 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0011292 and TRIM65 were upregulated, while miR-379-5p was downregulated in NSCLC tissues and cells. Circ_0011292 knockdown hindered NSCLC progression and enhanced PTX sensitivity of NSCLC. Circ_0011292 silencing reduced PTX resistance in vivo. Besides, miR-379-5p potentiated PTX sensitivity by targeting TRIM65. Also, circ_0011292 increased PTX resistance by sponging miR-379-5p. Conclusion: Circ_0011292 facilitated tumorigenesis and PTX resistance in NSCLC by regulating the miR-379-5p/TRIM65 axis, suggesting that circ_0011292 was a promising therapeutic target for NSCLC chemotherapy.