Long noncoding RNA DSCR8 promotes the proliferation of liver cancer cells and inhibits apoptosis via the miR-22-3p/ARPC5 Axis.

Emerging evidence shows that long noncoding RNAs (lncRNAs) play a vital role in the tumorigenesis and development of cancer, implying that some lncRNAs could be potential therapeutic targets. In this study, we employed Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to construct a ceRNA network by bioinformatic analysis, and the Down syndrome critical region 8 (lncRNA_DSCR8)/miR-22-3p/actin-related protein 2/3 complex subunit 5 (ARPC5) axis was identified as a potential target in liver cancer (LC). Next, we found that DSCR8 is highly expressed in LC cell lines Hep3B and Huh7. In addition, sh-DSCR8 inhibits cell proliferation and promotes cell apoptosis. Furthermore, we certified that DSCR8 serves as function as a sponge for miR-22-3p, while ARPC5 is a target gene of miR-22-3p, and the functions of DSCR8 promoting LC cell proliferation could be rescued by miR-22-3p. This study suggests that lncRNA_DSCR8 promotes LC progression and inhibits its apoptosis by regulating the miR-22-3p/ARPC5 axis, signifying that DSCR8 could be a novel therapeutic target for LC.

miR-124-3p Regulates FGF2-EGFR Pathway to Overcome Pemetrexed Resistance in Lung Adenocarcinoma Cells by Targeting MGAT5.

OBJECTIVE: To investigate whether miR-124-3p regulates the fibroblast growth factor 2 (FGF2)-epidermal growth factor receptor (EGFR) pathway by targeting MGAT5 to affect the pemetrexed resistance in lung adenocarcinoma cells. METHODS: PC9-MTA and H1993-MTA anti-pemetrexed lung adenocarcinoma cell lines were constructed. The cell viability of anti-pemetrexed and parent lung adenocarcinoma cells was analyzed using MTS assay and reverse transcription PCR to determine the expression of miR-124-3p. CCK8 assay, colony formation assay, and flow cytometry were used to determine cells' proliferation and apoptosis. FGF2-EGFR signaling pathway-related proteins and MGAT5 protein expression were quantified by Western blotting. The target relationship between miR-124-3p and MGAT5 was verified by double luciferase assay. A nude mouse model with a transplanted tumor was established using the anti-pemetrexed lung adenocarcinoma cells. Tumor volume and weight were determined, and the apoptosis of tumor cells was observed. RESULTS: The half-maximal inhibitory concentration of pemetrexed in anti-pemetrexed lung adenocarcinoma cells was higher than that in parent lung adenocarcinoma cells, and the expression of miR-124-3p in the anti-pemetrexed cells was lower than that of the parent cells. In the miR-124-3p overexpression group, MGAT5 silencing group, and miR-124-3p+MGAT5 overexpression group, compared with the control group, the proliferation ability of cells and tumors was markedly reduced; their apoptosis rates were increased significantly; expression levels of FGF2 and p-EGFR/EGFR were decreased; and the growth rate and tumor volume and mass were reduced; however, the opposite results were obtained in the miR-124-3p silencing group (p<0.05). CONCLUSION: miR-124-3p may inhibit the FGF2-EGFR pathway by targeting MGAT5 to decrease pemetrexed resistance in lung adenocarcinoma cells.