MRPL13 Act as a Novel Therapeutic Target and Could Promote Cell Proliferation in Non-Small Cell Lung Cancer

Abstract

Background:The latent involvement of MRPL13 in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to explore the role of MRPL13 in NSCLC. Methods: All analyses were performed in R software 4.0, SPSS version 23, and GraphPad Prism 8. The "limma" package was used to identify differentially expressed genes. Univariate and multivariate cox analyses were used to identify prognosis-related genes. A549 and H1299 lung cancer cell lines were selected for phenotypic experiments.Results: The high level of MRPL13 was correlated with poor T classification and overall survival. In vitro experiments showed that MRPL13 was highly expressed in NSCLC tissue and cell lines. MRPL13 knockdown inhibited the proliferation of lung cancer A549 and H1299 cell lines, which was further validated by in vivo experiment. Moreover, GSEA analysis suggested that the pathway of MYC target, PI3K/AKT/mTOR/ signaling, oxidative phosphorylation, and G2/M checkpoints may be the potential pathway where MRPL13 was involved. Meanwhile, MRPL13 demonstrated a negative correlation with M1 macrophage, CD8+ T cells, and CD4+ T cells, making it an underlying immunotherapy target of NSCLC. Conclusion: MRPL13 may promote the proliferation of NSCLC cells and serve as an independent tumor marker and an emerging therapeutic target.

Potential of Mitochondrial Ribosomal Genes as Cancer Biomarkers Demonstrated by Bioinformatics Results

“…Bioinformatic data analyses combined with in vitro and in vivo experimental results have revealed that MRPL13 is highly expressed in non-small cell lung cancer tissues and cell lines and can promote cancer cell proliferation; the locus is, therefore, an independent tumor marker and candidate therapeutic target (51). Expression levels of MRPS6, MRPS10, MRPS23, and MRPS31 are significantly elevated in breast cancer cells and tissues, and these findings have been corroborated by corresponding cell-based functional assay results (52,53).…”

MRPS16 promotes lung adenocarcinoma growth via the PI3K/AKT/Frataxin signalling axis

“…Linlin Liu et al 12 reported that the bioinformatics results provide evidence of the potential of mitochondrial ribosomal genes as cancer biomarkers. Annamaria Gal et al 13 and Wei Zhang et al 14 reported the strong correlation between mitochondrial translation genes and NSCLC prognosis. Wang et al 15 revealed that MRPS16 enhances tumour cell growth by PI3K/AKT signal path, demonstrating the critical role played by MRPS16 in biological processes further.…”

RNA binding protein: coordinated expression between the nuclear and mitochondrial genomes in tumors

“…By modulating mitochondrial translation, this dysregulation changes tumor metabolism and increases tumor heterogeneity, invasion, treatment resistance, and metastasis [ 31 , 42 ]. The high expression of MRPL15 and MRPL38 indicates poor prognosis in non-small cell lung cancer and ovarian cancer [ 43 , 44 ]. The expression of MRPL13 in breast cancer is significantly higher than that in normal tissues, and it can promote tumor cell proliferation and migration through the PI3K/Akt/mTOR signaling pathway [ 45 ].…”