Lung cancer characterized with malignant cell growth is the leading cause of cancer-related deaths. In recent years, several circular RNAs (circRNAs) have been reported to participate in lung cancer progression. However, the correlation between circular RNA (circRNA) and lung cancer still remains to be further investigated. In this study, we screened out a highly expressed circular RNA hsa(-)circRNA_103809 in lung cancer tissues. We showed hsa(-)circRNA(-)103809 could serve as a prognostic biomarker for patients with lung cancer. Furthermore, we found that hsa(-)circRNA(-)103809 knockdown significantly suppressed lung cancer cell proliferation and invasion in vitro and delayed tumor growth in vivo. In mechanism, we identified hsa(-)circRNA(-)103809 as a sponge of miR-4302 targeting ZNF121. By sequestering miR-4302, hsa(-)circRNA(-)103809 promoted the expression of ZNF121 which consequently enhanced MYC protein level in lung cancer cells. Through rescue assays, we demonstrated hsa(-)-circRNA(-)103809 contributed to lung cancer cell proliferation and invasion via facilitating ZNF121dependent MYC expression by sponging miR-4302. In conclusion, our findings illustrated a novel hsa (-)circRN(-)103809/miR-4302/ZNF121 /MYC reulatory signaling pathway in lung cancer progression. (C) 2018 Elsevier Inc. All rights reserved.