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Circular RNA hsa_circ_0004015 regulates the proliferation,invasion, and TKI drug resistance of non-small cell lung cancer by miR-1183/PDPK1 signaling pathway
Authors:You Zhou  Xiao Zheng  Bin Xu  Lujun Chen  Qi Wang  Haifeng Deng  Jingting Jiang
Institution:1. Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China;2. Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, 213003, China;3. Institute of Cell Therapy, Soochow University, Changzhou, 213003, China
Abstract:Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of Non-small cell lung cancer (NSCLC), however, the molecular mechanisms of circRNAs in cell proliferation, invasion and TKI drug resistance remain largely undetermined. Here, we identified hsa_circ_0004015 was upregulated in NSCLC tissues, and was associated with the poor overall survival rate of NSCLC patients. Knockdown of hsa_circ_0004015 significantly decreased cell viability, proliferation, and invasion, whereas overexpression exhibited opposed effects in vivo and in vitro. Furthermore, hsa_circ_0004015 could enhance the resistance of HCC827 to gefitinib. In mechanism, hsa_circ_0004015 acted as a sponge for miR-1183, and PDPK1 was revealed to be target gene of miR-1183. Subsequently, functional assays illustrated that the oncogenic effects of hsa_circ_0004015 was attributed to the regulation of miR-1183/PDPK1 axis. In conclusion, circ_0016760/miR-1183/PDPK1 signaling pathway might play vital roles in the tumorigenesis of NSCLC.
Keywords:Non-small cell lung cancer  hsa_circ_0004015  miR-1183  3-Phosphoinositide dependent protein kinase-1
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