[MiR-665 Promotes the Biological Behavior of Small Cell Lung Cancer by Targeting LLGL1].

BACKGROUND

MicroRNAs (miRNAs) are non-coding small molecule RNAs that are widely found in eukaryotic organisms, although some miRNAs have been found in tumors, the expression and effects of miR-665 on small cell lung cancer (SCLC) are unclear. The aim of this study was to analyze the effects of miR-665 on proliferation, cycle, invasion and migration of SCLC cells, and to explore the role of miR-665 in SCLC and its working mechanism.

METHODS

The expression of miR-665 in SCLC tissues and adjacent normal tissues was detected by qRT-PCR. TargetScan predicted potential target genes for miR-665 and validated with dual luciferase reporter assays, qRT-PCR and Western blot. CCK8 assay, flow cytometry, Transwell and wound healing assay to detect the effects of miR-665 and LLGL1 on proliferation, invasion, migration and S-phase fraction of SCLC cell line NCI-H446, NCI-H1688. A nude mouse xenograft model of SCLC was constructed and the effect of miR-665 on tumor growth in mice was observed.

RESULTS

The expression of miR-665 in SCLC tissues was significantly higher than that in non-tumor normal tissues. MiR-665 could target 3'-UTR of LLGL1 and inhibit its expression. Compared with non-tumor normal tissues, the expression of LLGL1 was significantly lower in SCLC tissues. Inhibition of miR-665 expression could inhibit proliferation, S-phase fraction, invasion and migration ability of SCLC NCL-H446 cells, and interference LLGL1 expression could reverse this inhibition effect. Up-regulation of miR-665 expression could promoted proliferation, S-phase fraction, invasion and migration ability of SCLC NCI-H1688 cells, but this promotion effect was also reversed by overexpression of LLGL1. In a nude mouse xenograft model of SCLC, inhibition of miR-665 expression could up-regulate LLGL1 protein expression and inhibit tumor growth, while up-regulation of miR-665 expression could produce opposite results.

CONCLUSIONS

The expression of miR-665 is closely related to SCLC. miR-665 can promote the biological behavior of SCLC cells by inhibiting the expression of target gene LLGL1, and miR-665 play a role in tumor-promoting genes in SCLC.