Leucine-rich repeat-containing G protein-coupled receptor 4 promotes proliferation, invasion and migration, and inhibits apoptosis in non-small cell lung cancer cells.

Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4/GPCR48) belongs to subfamily B of the GPCR superfamily. LGR4 is a transmembrane signaling molecule involved in organogenesis across multiple tissue systems and contributes to cancer progression. To the best of our knowledge, however, the specific involvement of LGR4/GPR48 in non-small cell lung cancer (NSCLC) has not been comprehensively studied. The present study aimed to elucidate the mechanisms by which LGR4 promotes the progression of NSCLC. First, the expression and survival of LGR4 were analyzed by downloading relevant data from The Cancer Genome Atlas database. Subsequently, immunohistochemistry was conducted to evaluate the association between LGR4 expression levels and prognostic outcomes in tissue samples from NSCLC. LGR4 levels were further determined across NSCLC cell line subtypes via western blotting and reverse transcription-quantitative PCR. LGR4 expression was silenced in the A549 and H226 cell lines using small interfering RNA. Flow cytometry, Cell Counting Kit-8 assays and Transwell assays were then used to study the effects on tumor cells after LGR4 knockdown. Finally, to elucidate the oncogenic mechanisms of LGR4, Gene Set Enrichment Analysis (GSEA) 4.3.3 software was utilized to identify signaling pathways potentially activated by the elevated expression of LGR4 in NSCLC tumor samples. The present findings indicated that LGR4 was significantly overexpressed in NSCLC and associated with worse clinical outcomes. Additionally, silencing LGR4 promoted apoptosis in A549 and H226 cells, while also suppressing cell proliferation, invasion and metastasis in NSCLC. Moreover, GSEA indicated that elevated expression of LGR4 in NSCLC may trigger activation of critical signaling pathways, such as the Wnt/β-catenin, TGF-β and PI3K/AKT/mTOR pathways. Therefore, LGR4 could represent a promising biomarker and a potential target for therapy in the management of NSCLC.