miR-378a-5p targets FGR to suppress proliferation, invasion and migration in lung adenocarcinoma cells.

Abstract

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Emerging evidence demonstrates that microRNAs (miRNAs) serve as crucial post-transcriptional regulators in lung carcinogenesis. Previous studies have identified aberrant expression of miR-378a-5p in non-small cell lung cancer (NSCLC), although its precise regulatory mechanisms remain to be fully elucidated. This study aimed to investigate the mechanisms by which miR-378a-5p leads to the onset and progression of lung adenocarcinoma (LUAD).

Methods: LUAD's miR-378a-5p expression levels were examined utilizing publicly accessible databases. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was used to measure the expression of miR-378a-5p in LUAD tissues and nearby normal tissues from the Affiliated Hospital of Nantong University. Additionally, A549 and H1299 cells were transfected with miR-378a-5p mimics and inhibitor, and the role of miR-378a-5p in cell proliferation, migration and invasion was evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound healing assay and transwell assay. The downstream target genes of miR-378a-5p were predicted using the microCosm database. Subsequently, the differentially expressed genes between the high and low expression groups of miR-378a-5p were subjected to enrichment analysis. The related pathways were identified, and the corresponding pathway-related genes were retrieved from the MsigDB website. The intersection of these genes was analyzed, leading to the identification of FGR proto-oncogene, Src family tyrosine kinase (FGR) as a potential downstream target gene. The expression level of FGR in LUAD was analyzed using the UALCAN database, and the correlation between FGR expression and various clinicopathological parameters was assessed. Immune infiltration analysis was performed based on the gene expression profiles of LUAD from The Cancer Genome Atlas (TCGA).

Results: It was discovered that LUAD tissues had downregulated miR-378a-5p. The miR-378a-5p inhibitor facilitated the proliferation, invasion, and migration, but the overexpression of miR-378a-5p turned out to limit these processes in both cell lines. Bioinformatics analysis identified FGR as a gene that miR-378a-5p targeted, with a positive correlation between their expression levels. Individuals with LUAD with low FGR expression had a poor prognosis, based upon research results of an analysis of the TCGA database. Furthermore, multivariate Cox regression analysis demonstrated that FGR was an independent prognostic factor for LUAD. According to the UALCAN database, FGR was revealed to be under expressed in LUAD tissues and to be substantially correlated with T stage. Furthermore, there were notable variations in the quantity of different immune categories of cells between the groups with high and low FGR expression.

Conclusions: By targeting FGR, miR-378a-5p prevents LUAD cell invasion, migration and proliferation.