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

Abstract

Next-generation sequencing and bioinformatics analyses have clearly revealed the roles of mitochondrial ribosomal genes in cancer development. Mitochondrial ribosomes are composed of three RNA components encoded by mitochondrial DNA and 82 specific protein components encoded by nuclear DNA. They synthesize mitochondrial inner membrane oxidative phosphorylation (OXPHOS)-related proteins and participate in various biological activities via the regulation of energy metabolism and apoptosis. Mitochondrial ribosomal genes are strongly associated with clinical features such as prognosis and foci metastasis in patients with cancer. Accordingly, mitochondrial ribosomes have become an important focus of cancer research. We review recent advances in bioinformatics research that have explored the link between mitochondrial ribosomes and cancer, with a focus on the potential of mitochondrial ribosomal genes as biomarkers in cancer.

Keywords: apoptosis; bioinformatics; biomarker; cancer; energy metabolism; mitochondrial ribosome.

Figure 1

Composition and structure of the mitochondrial ribosome. The mature mitochondrial ribosome, which consists of a large and a small subunit, is permanently anchored to the inner mitochondrial membrane by MRPL45 (mL45) of the large subunit. Mitochondrial ribosomal proteins are synthesized within the cytosol and enter mitochondria mediated by the transmembrane transport complex including Translocase of the Outer mitochondrial Membrane (TOM) and Translocase of the Inner Membrane (TIM). RNA components are encoded by mitochondrial DNA.

Figure 2

Function of the mitochondrial ribosome. Mitochondrial ribosomes synthesize the subunit proteins of OXPHOS complex I, III, IV and V, which are encoded by the mitochondrial DNA. The dashed black line represents the flow of electrons.

Figure 3

Expression of MRPS29, MRPS30, MRPL41 across TCGA cancers. Three representative mitochondrial ribosomal genes are differentially expressed in cancer. TPM is the normalization of gene reads derived from high-throughput sequencing (39). (*p < 0.05; **p < 0.01).TPM, Transcripts Per Kilobase Million; BLCA, Bladder urothelial carcinoma; BRCA, Breast invasive carcinoma; CESC, Cervical squamous cell carcinoma; CHOL, Cholangiocarcinoma; COAD, Colon adenocarcinoma; ESCA, Esophageal carcinoma; GBM, Glioblastoma multiforme; HNSC, Head and Neck squamous cell carcinoma; KICH, Kidney Chromophobe; KIRC, Kidney renal clear cell carcinoma; KIRP, Kidney renal papillary cell carcinoma; LIHC, Liver hepatocellular carcinoma; LUAD, Lung adenocarcinoma; LUSC, Lung squamous cell carcinoma; PAAD, Pancreatic adenocarcinoma; PRAD, Prostate adenocarcinoma; PCPG, Pheochromocytoma and Paraganglioma; READ, Rectum adenocarcinoma; SARC, Sarcoma; SKCM, Skin Cutaneous Melanoma; THCA, Thyroid carcinoma; THYM, Thymoma; STAD, Stomach adenocarcinoma; UCEC, Uterine Corpus Endometrial Carcinoma.