Aberrant mitochondrial homeostasis at the crossroad of musculoskeletal ageing and non-small cell lung cancer

Abstract

Cancer cachexia is accompanied by muscle atrophy, sharing multiple common catabolic pathways with sarcopenia, including mitochondrial dysfunction. This study investigated gene expression from skeletal muscle tissues of older healthy adults, who are at risk of age-related sarcopenia, to identify potential gene biomarkers whose dysregulated expression and protein interference were involved in non-small cell lung cancer (NSCLC). Screening of the literature resulted in 14 microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880 in musculoskeletal ageing; GSE118370, GSE33532, GSE19804, GSE18842, GSE27262, GSE19188, GSE31210, GSE40791 in NSCLC). Differentially expressed genes (DEGs) were used to construct protein-protein interaction networks and retrieve clustering gene modules. Overlapping module DEGs were ranked based on 11 topological algorithms and were correlated with prognosis, tissue expression, and tumour purity in NSCLC. The analysis revealed that the dysregulated expression of the mammalian mitochondrial ribosomal proteins, Mitochondrial Ribosomal Protein S26 (MRPS26), Mitochondrial Ribosomal Protein S17 (MRPS17), Mitochondrial Ribosomal Protein L18 (MRPL18) and Mitochondrial Ribosomal Protein L51 (MRPL51) were linked to reduced survival and tumour purity in NSCLC while tissue expression of the same genes followed an opposite direction in healthy older adults. These results support a potential link between the mitochondrial ribosomal microenvironment in ageing muscle and NSCLC. Further studies comparing changes in sarcopenia and NSCLC associated cachexia are warranted.

MRPL51 is a downstream target of FOXM1 in promoting the malignant behaviors of lung adenocarcinoma

“…However, the involvement of MRPL51 in carcinogenesis remains poorly understood. The upregulation of MRPL51 in lung cancer was observed in a previous study ( 10 ), which may be related to gene promoter hypomethylation ( 31 ). In addition, MRPL51 is a nitric oxide (NO)-inducible gene in NSCLC cells, with >5-fold upregulation post-NO treatment ( 32 ).…”

“…Upregulation of MRPL52 is associated with aggressive clinicopathological features (such as higher histological grade, lymph node metastasis, and increased tumor size), and contributes to malignant behaviors, including epithelial-mesenchymal transition (EMT), migration and invasion of breast cancer cells ( 9 ). A recent bioinformatics study analyzed the shared dysregulated genes of musculoskeletal aging and NSCLC, and revealed that MRPL51 is among the shared genes ( 10 ). Therefore, it is necessary to explore how MRPL51 regulates the malignant behaviors of LUAD.…”

Identification of mitochondria-related biomarkers in childhood allergic asthma

“…Mammalian mitochondrial ribosomal protein MRPS26 expression levels are correlated with tumor purity in non-small cell lung cancer (NSCLC). MRPS26 has been observed to participate in mitochondrial activity of muscle stem cells [ 30 ]. MTIF3 encodes 29 kDa proteins that promote the formation of initiation complexes on mitochondrial 55 S ribosomes and play an active role in translation initiation.…”

Identification of mitochondria-related biomarkers in childhood allergic asthma

“…Mammalian mitochondrial ribosomal protein MRPS26 expression levels are correlated with tumor purity in non-small cell lung cancer (NSCLC). MRPS26 has been observed to participate in mitochondrial activity of muscle stem cells [30]. MTIF3 encodes 29 kDa proteins that promote the formation of initiation complexes on mitochondrial 55S ribosomes and play an active role in translation initiation.…”