LncRNA HOST2 enhances gefitinib-resistance in non-small cell lung cancer by down-regulating miRNA-621.

ABSTRACT

OBJECTIVE: The aim of this study was to clarify whether long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) could enhance gefitinib-resistance in non-small cell lung cancer (NSCLC) by down-regulating microRNA-621 (miRNA-621). MATERIALS AND METHODS: The relative expression levels of HOST2, miRNA-621 and SYF2 in NSCLC cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The regulatory effects of HOST2 and miRNA-621 on the proliferative ability and cell cycle of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Meanwhile, the binding relationship between miRNA-621 to HOST2 and SYF2 was verified by Dual-Luciferase reporter gene assay. Furthermore, rescue experiments were conducted to verify whether HOST2 regulated the proliferative ability and cell cycle of NSCLC cells by absorbing miRNA-621 to up-regulate SYF2 level. RESULTS: HOST2 showed significantly greater abundance in gefitinib-resistant PC9 cells (PC9/GR) relative to parental cells. The up-regulation of HOST2 markedly enhanced gefitinib-resistance, the proliferative ability and cell cycle progression of PC9 cells. Subsequent Dual-Luciferase reporter gene assay showed the binding relationship between HOST2 and miRNA-621. Moreover, miRNA-621 was lowly expressed in PC9/GR cells compared with parental cells. Up-regulation of miRNA-621 significantly suppressed the proliferative ability and cell cycle progression, as well as reversed gefitinib-sensitivity of PC9 cells. More importantly, miRNA-621 up-regulation abolished the biological function of HOST2 in NSCLC. SYF2 was confirmed as the target gene of miRNA-621 in the same way. In addition, the overexpression of SYF2 remarkably enhanced gefitinib-resistance, while reversed the inhibitory effects of miRNA-621 on the proliferative ability and cell cycle of NSCLC cells. CONCLUSIONS: HOST2 elevates gefitinib-resistance in NSCLC by degrading miRNA-621 to upregulate SYF2.