A Metabolic Phenotype Based on Mitochondrial Ribosomal Protein Expression as a Predictor of Lymph Node Metastasis in Papillary Thyroid Carcinoma

Lee, Jandee; Seol, Mi Youn; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang–Wook; Jeong, Jong Ju; Shin, Dong Yeob; Nam, Kee Hyun; Lee, Mi Kyung; Chung, Woong Youn; Jo, Young Suk

doi:10.1097/md.0000000000000380

Cited by 25 publications

(24 citation statements)

References 31 publications

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“…In an attempt to identify genes and pathways associated with mortality in PTC, Nilubol et al (2011) performed genome-wide expression (GWE) analysis in 64 PTC patients and identified the oxidative phosphorylation pathway as one of the significantly perturbed pathways. In addition, Lee and colleagues also showed that the expression of OxPhos gene sets was significantly lower in primary PTC than in matched normal thyroid tissue (Lee et al, 2015a). Our findings revealed a similar trend with OxPhos genes being significantly downregulated in PTCs versus normal thyroid tissues as well as in PTC LNM-P versus PTC LNN.…”

Section: Discussionsupporting

confidence: 82%

“…However, significant enrichment of OxPhos pathway was only observed in PTC LNM-P compared to PTC LNN. Alteration in metabolic processes has been considered as an indispensable component of malignant transformation (Lee et al, 2015a) thus the involvement of oxidative phosphorylation in LNM in PTC necessitates further investigation. Oxidative phosphorylation is a process whereby an adenosine triphosphate (ATP) is produced as a result of electrons transfer from nicotinamide adenine dinucleotide (NADH) or flavin-adenine dinucleotide (FADH 2 ) to oxygen by a series of electron carriers (Berg et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Peer Review #2 of "Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis (v0.1)"

2016

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis (v0.1)"

2016

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“…Interestingly, a recent study revealed that MRPS39, also called PTCD3, played a critical role in Mycdriven lymphoma (31). In addition, MRPL44 expression was identified as a representative marker of a metabolic phenotype, and it was predictive of lymph node metastasis in papillary thyroid carcinoma (32). Those results suggested that detailed studies on the link between the mitoribosome and cancer activity may extend our understanding of novel molecular and metabolic mechanisms involved in tumor development.…”

Section: Mitochondria Ribosomal Defect Promotes Cell Invasivenessmentioning

confidence: 93%

Lactate-mediated mitoribosomal defects impair mitochondrial oxidative phosphorylation and promote hepatoma cell invasiveness

Lee

Lim

Jeoun

et al. 2017

Journal of Biological Chemistry

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Impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of mitochondrial ribosomal protein L13 (MRPL13), a mitochondrial ribosome (mitoribosome) subunit, suggesting a ribosomal defect. Specific inhibition of mitoribosomal translation by doxycycline, chloramphenicol, or siRNA-mediated MRPL13 knockdown decreased mitochondrial protein expression, reduced oxygen consumption rate, and increased CLN1-mediated tumor cell invasiveness in SNU387 cells, which have active mitochondria. Interestingly, we also found that exogenous lactate treatment suppressed MRPL13 expression and oxygen consumption rate and induced CLN1 expression. A bioinformatic analysis of the open RNA-Seq database from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) cohort revealed a significant negative correlation between MRPL13 and CLN1 expression. Moreover, in patients with low MRPL13 expression, two oxidative metabolic indicators, pyruvate dehydrogenase B expression and the ratio of lactate dehydrogenase type B to type A, significantly and negatively correlated with CLN1 expression, indicating that the combination of elevated glycolysis and deficient MRPL13 activity was closely linked to CLN1-mediated tumor activity in LIHC. These results suggest that OXPHOS defects may be initiated and propagated by lactate-mediated mitoribosomal deficiencies and that these deficiencies are critically involved in LIHC development.

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“…22 More importantly, many studies have reported other functions of MRPs in tumorigenesis. [23][24][25] For example, MRPS23, a member of the MRP family, has been demonstrated to be aberrantly expressed in some types of cancers and closely associated with development of these cancers. [26][27][28] However, the biological functions of MRPS23 in OS remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells

Liu

Wang

et al. 2019

RSC Adv.

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Mitochondrial ribosomal protein S23 (MRPS23), encoded by a nuclear gene, is a participant in the translation of mitochondrial proteins. Recently, MRPS23 has been reported to be overexpressed in many types of cancers and have a close association with cancer progression. However, the specific roles of MRPS23 in osteosarcoma (OS) remain unknown. In this study, we investigated the expression pattern and biological functions of MRPS23 in OS cells. Our results demonstrated that MRPS23 was up-regulated in OS tissues and cell lines. Down-regulation of MRPS23 significantly inhibited OS cell proliferation and invasion induced by lipopolysaccharide (LPS) in vitro. Furthermore, the in vivo experiments showed that MRPS23 down-regulation markedly suppressed OS cell growth and metastasis induced by LPS. Mechanistically, down-regulation of MRPS23 inhibited the activity of NF-kB signaling pathway in OS cells. In conclusion, these findings indicated that MRPS23 may be a potential therapeutic target for OS treatment. Results Expression of MRPS23 is elevated in OS tissues and cell linesThe expression of MRPS23 in OS tissues was examined by immunohistochemistry, RT-PCR and western blot analysis. The

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A Metabolic Phenotype Based on Mitochondrial Ribosomal Protein Expression as a Predictor of Lymph Node Metastasis in Papillary Thyroid Carcinoma

Abstract: Supplemental Digital Content is available in the text

Cited by 25 publications

References 31 publications

Peer Review #2 of "Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis (v0.1)"

Peer Review #2 of "Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis (v0.1)"

Lactate-mediated mitoribosomal defects impair mitochondrial oxidative phosphorylation and promote hepatoma cell invasiveness

Down-regulation of MRPS23 inhibits LPS-induced proliferation and invasionviaregulation of the NF-κB signaling pathway in osteosarcoma cells

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