Long non-coding RNA LINC00511 promotes proliferation, invasion, and migration of non-small cell lung cancer cells by targeting miR-625-5p/GSPT1.

BACKGROUND

Lung cancer is a malignant tumor with a high rate of mortality and metastasis. Recently, extensive research has shown that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of non-small cell lung cancer (NSCLC). In this paper, we aimed to explore the impact of long intergenic non-coding RNA 00511 (LINC00511) on the development and metastasis of NSCLC.

METHODS

A dataset containing 501 lung squamous cell carcinoma (LUSC) samples and 49 normal samples was downloaded from The Cancer Genome Atlas (TCGA). The differential gene expression and prognostic potential of LINC00511 in LUSC were analyzed by "limma" in R software. Samples of tumor tissues and normal tissues from 67 patients with NSCLC were obtained, along with clinical features. NSCLC cell proliferation, cell cycle, migration, and invasion were detected by LINC00511 knockdown with Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing assay, and Transwell experiment. The regulatory relationship between LINC00511 and microRNA (miR)-625-5p, or between miR-625-5p and G1 to S phase transition 1 (GSPT1), was detected by luciferase reporter gene assay. LINC00511, miR-625-5p, and GSPT1 expression in tumor and normal tissues and cells was determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. A xenograft experiment in nude mice was performed. Ki67 and GSPT1 expression in the tumor tissues of the nude mice was assessed by immunohistochemistry.

RESULTS

LINC00511 expression was clearly higher in the tumor tissues of the NSCLC patients than in normal tissues (P<0.001). High LINC00511 expression was related to larger tumor size, positive lymph node metastasis, advanced TNM stage, and a lower 5-year survival rate. Compared with those of the shNC group, the NSCLC cells of the shLINC00511 group had a prominently lower optical density (OD) 450 value at 72 h, a lower percentage of cells in S phase, a higher relative wound width, and a lower invasive cell number (P<0.01 or P<0.001). LINC00511 promoted GSPT1 expression via suppressing miR-625-5p. Compared with those of the shNC group, the nude mice of the shLINC00511 group had a much lower subcutaneous tumor volume and weight (P<0.05 or P<0.001).

CONCLUSIONS

lncRNA LINC00511 promotes proliferation, invasion, and migration of NSCLC cells by targeting miR-625-5p/GSPT. LINC00511 may be a potential diagnostic marker and therapeutic target for NSCLC.