Dysregulated LINC00961 Contributes to the Vitality and Migration of NSCLC Via miR-19a-3p/miR-19b-3p/miR-125b-5p

摘要

Accumulating evidence implies that long noncoding RNAs participate in non-small cell lung cancer (NSCLC) tumorigenesis. Our current study synthetically analyzed RNA sequencing data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We identified LINC00961 significantly downregulated in NSCLC tissues. We explored the LINC00961 expression in NSCLC tumor tissues and cell lines with reverse transcription-quantitative polymerase chain reaction analysis. Lentivirus-mediated infection upregulated the expression of LINC00961 in A549 cells. The proliferation and migration capability were also measured in A549 cells. In addition, we performed luciferase reporter gene assay to investigate whether LINC00961 directly interacts with miR-19a-3p/miR-19b-3p/miR-125b-5p. A nude mice model was used to detect the potential biological process of LINC00961 on tumor growth in vivo. The results showed that LINC00961 was significantly down-egulated in NSCLC tissues and cell lines. LV-LINC00961 effectively increased the expression of LINC00961 and decreased the expression of miR-19a-3p/miR-19b-3p/miR-125b-5p. LINC00961 upregulation remarkably inhibited cell proliferation, migration, and invasion while promoting cell apoptosis in A549 cells. Luciferase reporter gene assay revealed that LINC00961 could directly sponge miR-19a-3p/miR-19b-3p/miR-125b-5p. Moreover, overexpressed miR-19a-3p/miR-19b-3p/miR-125b-5p reversed the effect of LINC00961 on cell function of A549 cells. Western blot assays revealed that LINC00961 could partially act as a tumor suppressor via affecting PI3K-AKT/MAPK/mTOR signaling pathway. In addition, overexpressed LINC00961-inhibited tumor growth was demonstrated in vivo. Overexpression of LINC00961 inhibited cell viability, invasion, and induced apoptosis in NSCLC, potentially via suppressing the expression of miR-19a-3p/miR-19b-3p/miR-125b-5p by targeting PI3K-AKT/MAPK/mTOR signaling pathways, which might provide the potential biomarker for NSCLC diagnosis and therapies.