Human non-small cell lung cancer (NSCLC) is an inflammation-related disease. Although IL-17-induced NSCLC cell proliferation that can be regulated by transcription factors has been demonstrated, the role and mechanism of other regulatory molecules, such as long noncoding RNAs (lncRNAs), in cell proliferation remains unclear. In this study, we screened and verified the expression of aberrant lncRNAs in NSCLC cell lines (H1299 and PC9) stimulated with IL-17, and found that LINC01518 was not only overexpressed, but also enhanced cell proliferation through IL-17/IL-17RA. Further mechanism investigation discovered that IL-17-upregulated LINC01518 was mainly localized in the cytoplasm, and it could combine with miR-20a-5p through a "sponge" function, decreasing miR-20a-5p induction, while LINC01518 and miR-20a-5p co-overexpression could partially reverse the cell proliferation mediated by LINC01518 alone. LINC01518 increase or miR-20a-5p decrease could elevate E2F1 level boosting H1299 cell proliferation exposed to IL-17, while miR-20a-5p and E2F1 co-overexpression partially restored the cell proliferation inhibition from miR-20a-5p upregulation. Besides, the xenograft tumor experiments of mice confirmed that LINC01518 overexpression indeed promoted tumor growth, cell proliferation, miR-20a-5p downregulation, and E2F1 upregulation. While LINC01518 knockdown reduced tumor growth, cell proliferation, miR-20a-5p downregulation, and E2F1 upregulation induced by IL-17 stimulation. Taken together, these findings reveal that the LINC01518/miR-20a-5p/E2F1 axis contributes to IL-17-induced cell proliferation in NSCLC.
Zhao et al. (Thu,) studied this question.