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The Molecular Mechanism of Circular RNA Molecule CircSETD3 in Gefitinib Acquired Resistance in Non-Small Cell Lung Cancer

Author(s): Jing Su, J. Zhao, Ning Zhang, B. Xiang, Xuejun Zhi and Y. Huo*
Department of Respiratory Medicine, The First Affiliated Hospital of Hebei North University, 1Department of Anatomy, School of Basic Medicine, Hebei North University, Zhangjiakou, Hebei 075000, China

Correspondence Address:
Y. Huo, Department of Anatomy, School of Basic Medicine, Hebei North University, Zhangjiakou, Hebei 075000, China, E-mail:

To explore the molecular pathway of the circular RNA molecule in gefitinib acquired resistance in nonsmall cell lung cancer and to provide a new therapeutic direction for clinical treatment of non-small cell lung cancer. The gefitinib-sensitive non-small cell lung cancer cell strain H292_S was selected to construct gefitinib acquired resistant cell model H292_R. Also, the overexpression group and vector control group of H292_S transfected circSETD3; the knockdown plasmid group and vector control group of H292_R transfected circSETD3 were prepared. The degree of cell response to gefitinib was measured by Western blotting and cell counting kit-8 method. The RNA sequencing method was used to screen differentially expressed circular RNA in cells and real-time fluorescent quantitative polymerase chain reaction was used to verify the sequencing results; the dual-luciferase report was used to screen and verify the relationship between circSETD3 and microRNA-520h. After the drug-resistant H292_R cell strain was processed by gefitinib, the expression of phosphorylated epidermal growth factor receptor, phosphatidylinositol 3-kinase and protein kinase B decreased significantly. The expressions of three circular RNAs in has_circ_0000567, has_circ_0000655 and has_circ_0006867, were all up-regulated in drug-resistant strains, and the differences were statistically significant (p<0.05). The overexpression group of circSETD3 had a significant effect on the growth and reproduction ability of cells (p<0.05); the wild type group of the dual-luciferase report plasmid was transfected into 293T cells together with microRNA-520h mimics and the fluorescence intensity decreased significantly (p<0.05). In addition, if the luciferase reporter plasmid mutant group (mutant) was transfected into 293T cells together with microRNA-520h mimics, the fluorescence intensity would not change significantly. circSETD3 could be directly bound to microRNA-520h.

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Citations : 66710

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