Background: Numerous studies show that long non-coding RNAs take important roles in human cancer progression. Although zebrafish xenograft become a novel in vivo model for human cancer research recently, whether it can be used for studying the function of lncRNAs remains unknown.Methods: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies by using zebrafish xenograft also confirmed these roles of LINC00152. In vivo confocal

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... aging was also used to evaluate the function of LINC00152 in cell proliferation and migration more accurately. Pharmacology experiments were further performed to study the potential tumor treatment of LINC00152 downregulation combined with EGFR inhibitor in cultured cells and zebrafish xenograft.Results: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro . In zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells by two imaging methods at different magnification. Moreover, knocking-down LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and zebrafish xenograft model.Conclusion: Our study reveals the oncogenic roles and potential tumor treatment target of LINC00152 in lung cancer cells by zebrafish xenograft models, suggesting that this model could be used for the functional and application study of human lncRNA in tumor biology.* Wenyi Shen and Juan Pu contributed equally to this work.