miR-6742-5p regulates the invasion and migration of lung adenocarcinoma cells via mediating FGF8/ERK12/MMP9/MMP2 signaling pathway

Abstract

Background: microRNAs (miRNAs) are involved in the progression of Lung adenocarcinoma (LUAD), however, the functions of miR-6742-5p in LUAD remains unknown, thereby this study was carried on. Methods: The mRNA and miRNA expression data from the LUAD and normal control were obtained from Gene Expression Omnibus (GEO) database, TargetScan and mirDIP were applied to predict the relationship between miR-6742-5p and FGF8.Q-PCR, western blot, dual-luciferase, wound Healing and transwell assays were performed to test the functions of miR-6742-5p in LUAD. Results: Bioinformatics analysis and dual-luciferase identified FGF8 is the target-gene of miR-6742-5p, which is declined in LUAD of human tissues and cell lines, and miR-6742-5P OE suppressed the progression of LUAD in nude mice. MiR-6742-5p OE and KD suppressed or increased the abilities of LUAD' metastasis tested by wound healing and transwell assays H522 and PC-9 cells, these effects about miR-6742-5p OE were reversed by FGF8; miR-6742-5p OE, KD inhibited and increased the expression of FGF8 as its downstream p-ERK1/2, MMP-2/-9, these results were corrected by ERK1/2 inhibitor: Ro 67-7476; the miR-6742-5p KD increased the migrated and invaded cells and suppressed by MMPs inhibitor: S3304. These results identified the negative correlation of miR-6742-5p with FGF8-ERK1/2 signal pathway in LUAD progression. Conclusions: We conclude that miR-6742-5p might be a regulator of LUAD progression by targeting FGF8/ERK1/2/MMPs signaling pathway, which provides a novel therapeutic target for LUAD. ETHICAL STATEMENTAll animal experiments were approved by Research Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-R327).

Immunohistochemical Features of MMP-9 and pSTAT1 in Granuloma Annulare and Sarcoidosis: A Comparative Study of 62 Cases

“…In our study, we examined the expression of pSTAT1, a molecule expressed in macrophages to respond to lymphocytes. Previous studies have demonstrated the contribution of gelatinase MMP-2 and MMP-9 in cell migration [ 21 ], and we explored the role of MMP-9 in macrophage recruitment in GA and sarcoidosis.…”

MicroRNA‑mediated regulation in lung adenocarcinoma: Signaling pathways and potential therapeutic implications (Review)

“…MiR-6742-5p, miR-363-3p, miR-451 and miR-1258 are expressed at low levels in LUAD and inhibit cell proliferation. Mechanistically, they reduced the phosphorylation of the ERK1/2 protein through the ERK pathway, which is considered a classic branch of the MAPK signaling pathway (127,145,152,157). By contrast, miR-1307-5p and miR-25 participated in the regulation of LUAD as oncogenes through the ERK signaling pathway (127,159).…”