Abstract
BackgroundNumerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown.MethodsIn vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model.ResultsSilencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro. In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model.ConclusionOur study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.
Highlights
Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression
After 48 h posttransfection, we observed that the knockdown efficiency of LINC00152 was 81.5% in SPCA1 cells and 91.9% in A549 cells compared with the negative control small interfering RNA (siRNA) (Fig. 1b, c)
These results verified the oncogenic roles of LINC00152 in the two lung cancer cell lines, suggesting that we could perform further in vivo tests in zebrafish xenografts using this siRNAmediated knockdown strategy
Summary
Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown. Recent studies showed that lncRNAs play critical roles in proliferation, differentiation, metastasis, metabolism, and apoptosis in cancer progression by regulating the expression of protein-coding genes at the transcriptional, posttranscriptional and epigenetic levels [12,13,14,15,16]. Zebrafish xenograft models offer the in vivo conditions of human cancer cells and do not have such restrictions, which prompts us to explore whether such models can be used to study the roles of human lncRNAs in cancer
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