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Abstract: CASZ1, a zinc finger transcription factor with two isoforms, is known to play important roles in cardiac and neural development. The abnormal expression of CASZ1 is also frequently found in a variety of tumors but has different effects on different tumors; for example, it acts as a tumor suppressor in neuroblastoma but promotes cancer metastasis in ovarian cancer. However, the effect of CASZ1 in lung cancer, the most lethal cancer, remains unclear. Here, we found that the expression of CASZ1 in lung cancer is positively associated with cancer metastasis and poor prognosis. The overexpression of CASZ1b promotes lung cancer cell migration, invasion, and epithelialmesenchymal transition and is associated with poor prognosis in lung cancer patients. The knockdown of CASZ1 resulted in the suppression of epithelial-mesenchymal transition, migration, and invasion of lung cancer cells and reduced metastasis in vivo. The results of an RNA-sequencing analysis of CASZ1-silenced cells showed that CASZ1 considerably affected the integrin-mediated pathways. CASZ1 bound to the ITGAV promoter and transcriptionally regulated ITGAV expression. Our findings demonstrate that CASZ1 plays an oncogenic role in lung cancer and that CASZ1 promotes lung cancer migration, invasion and metastasis is mediated by ITGAV.

Keywords: Lung cancer, epithelial-mesenchymal transition, metastasis, integrin alpha V (ITGAV)