MRPL51 expression is associated with poor prognosis and regulates lung adenocarcinoma progression via neurotensin.

BACKGROUND: The expression levels of mitochondrial ribosomal proteins (MRPs) are closely associated with the clinicopathological characteristics of various tumors and play a critical role in the initiation and progression of malignancies. Mitochondrial ribosomal protein L51 (MRPL51), a member of the MRP family, has not been well characterized in lung adenocarcinoma (LUAD). Elucidating the clinical significance of MRPL51 expression is essential, as it may not only provide valuable prognostic insights but also highlight its potential as a therapeutic target. Such findings could strengthen the rationale for clinical translational research and help bridge the gap between fundamental mechanisms and clinical application. This study investigates the role and underlying mechanisms of MRPL51 in the initiation and progression of lung adenocarcinoma. The findings aim to offer novel insights and robust scientific evidence for the identification of prognostic biomarkers and the development of targeted therapeutic strategies for this malignancy. METHODS: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, along with immunohistochemistry (IHC), were used to analyze the expression of MRPL51 in LUAD and its correlation with clinical characteristics. Prognostic data from clinical patients were collected and examined in combination with IHC scores to assess the potential of MRPL51 as a prognostic biomarker. The A549 LUAD cell line was selected, and MRPL51 expression was modulate, with overexpression and CRISPR/Cas9 lentiviral vectors being used for interference. In vitro and in vivo gene function studies were conducted with cell functional assays, molecular biological techniques, and nude mouse models. Next-generation sequencing (NGS) and R-based bioinformatics analysis were performed to identify the MRPL51-associated signaling pathways and key molecules. RESULTS: MRPL51 was upregulated in LUAD and correlated with tumor T stage, N stage, and American Joint Committee on Cancer stage. Elevated expression of MRPL51 was associated with poor patient prognosis, and knockout of MRPL51 significantly inhibited the proliferation, colony formation, and invasion of LUAD cells while also slowing the growth of LUAD xenografts. Conversely, overexpression of MRPL51 modestly enhanced the proliferative capacity of LUAD cells. Moreover, MRPL51 may promote the malignant biological behaviors of LUAD cells through neurotensin (NTS) and its downstream EGFR/PI3K/AKT signaling axis. CONCLUSIONS: MRPL51 is upregulated in LUAD and associated with poor prognosis, potentially driving progression via the downstream molecule NTS.