Iron-sulphur cluster biogenesis factor LYRM4 is a novel prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma

Pang, Yilin; Tan, Guoqiang; Yang, Xunjun; Lin, Yuanshan; Chen, Yao; Zhang, Jinping; Xie, Ting; Zhou, Huaibin; Fang, Jun; Zhao, Qiongya; Ren, Xiaojun; Li, Jianghui; Lyu, Jianxin; Wang, Zheng

doi:10.1186/s12935-021-02131-3

Cited by 8 publications

(11 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in vitro experiments with HCC showed that ACO2 expression was significantly increased in HCC cells compared with hepatic cells, which was consistent with the result of Yilin Pang et al. ( 47 ). Our experimental results first revealed that ACO2 acted as an oncogene and promoted the growth, migration, and invasiveness of HCC cells.…”

Section: Discussionsupporting

confidence: 90%

Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma

et al. 2022

View full text Add to dashboard Cite

BackgroundRecent evidence increasingly suggests key roles for the tricarboxylic acid cycle and fatty acid metabolism in tumor progression and metastasis. Aconitase 2 (ACO2) is a component of the tricarboxylic acid cycle and represents a key cellular metabolic hub that promotes de novo fatty acid biosynthesis. However, there have been few reports on the role of ACO2 in tumorigenesis and cancer progression.MethodsThrough the comprehensive use of datasets from The Cancer Genome Atlas, Genotype-Tissue Expression Project, cBioPortal, Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, DNA Methylation Interactive Visualization Database, and TIMER2, we adopted bioinformatics methods to uncover the potential carcinogenic roles of ACO2, including by analysing ACO2 expression and correlations between prognosis, genetic mutations, immune cell infiltration, DNA methylation, tumor mutational burden, and microsatellite instability in different tumors. Additionally, the expression level and tumor-promoting effect of ACO2 were verified in hepatocellular carcinoma (HCC) cells. To explore the underlying mechanisms of ACO2 in human cancer, ACO2-related gene enrichment analysis and lipid metabolomics were performed using LM3 cells with or without ACO2 knockdown.ResultsThe results indicated that ACO2 was highly expressed in most cancers, showing early diagnostic value in six tumor types, and was positively or negatively associated with prognosis in different tumors. Moreover, ACO2 expression was associated with immune cell infiltration, such as CD8+ T cells and tumor-associated neutrophils, in some cancers. For most cancer types, there was a significant association between immune checkpoint-associated genes and ACO2 expression. Compared with normal hepatocytes, ACO2 was upregulated in HCC cells, which promoted their proliferation and migration. Furthermore, to explore the underlying molecular mechanism, we performed KEGG pathway enrichment analysis of ACO2-associated genes and lipidomics using LM3 cells with or without ACO2 knockdown, which screened 19 significantly altered metabolites, including 17 with reduced levels and 2 with increased levels.ConclusionThrough pan-cancer analysis, we discovered for the first time and verified that ACO2 could be a useful diagnostic biomarker for cancer detection. Additionally, ACO2 could be used as an auxiliary prognostic marker or as a marker for immunotherapy in some tumor types.

show abstract

Section: Discussionsupporting

confidence: 90%

Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Moreover, induced by the E 2 /ER pathway [80], the general transcription factors NRF1/2, Sp1, and YY1 can activate the transcription of NDUFS8. LYRM4 [81], long non-coding RNA PPP1R14B-AS1 [82], and decitabine [83] can also increase NDUFS8 expression in some cancer cells. Abbreviations: NDUFS8: NADH:ubiquinone oxidoreductase core subunit S8; ROS: Reactive Oxygen Species; GPX4: Glutathione peroxidase 4; EMT: epithelial-mesenchymal transition; MEK1/2: mitogen-activated protein kinase kinases 1/2; ERK1/2: extracellular signal-regulated kinase 1/2; STATs: signal transducers and activators of transcription; JNK: c-Jun N-terminal kinase; E 2 : estrogen; ER: estrogen receptor; NRF1/2: nuclear respiratory factor 1/2; Sp1: Specificity Protein 1; YY1: Yin Yang 1; LYRM4: LYR (leucine/tyrosine/arginine) motif protein 4.…”

Section: Ndufs8 and Cancermentioning

confidence: 99%

Section: Ndufs8 and Cancermentioning

confidence: 99%

“…The elevated NDUFS8 could also be found in hepatocellular carcinoma (HCC) [81], which was associated with the dedifferentiation of HCC [88]. Likewise, the rise of NDUFS8 in HCC was modulated by LYR (leucine/tyrosine/arginine) motif protein 4 [81], helping HCC cells avoid sorafenib and successfully survive [89]. A combination of lung adenocarcinoma and liver cancer showed that NDUFS8 was overexpressed as well and positively related to long non-coding RNA PPP1R14B-AS1, promoting tumor cell proliferation and migration via the enhancement of mitochondrial respiration [82].…”

Section: Ndufs8 and Cancermentioning

confidence: 99%

“…Moreover, induced by the E2/ER pathway[80], the general tra scription factors NRF1/2, Sp1, and YY1 can activate the transcription of NDUFS8. LYRM4[81], lon non-coding RNA PPP1R14B-AS1[82], and decitabine[83] can also increase NDUFS8 expression some cancer cells. Abbreviations: NDUFS8: NADH:ubiquinone oxidoreductase core subunit S…”

mentioning

confidence: 99%

See 2 more Smart Citations

Emerging Roles of NDUFS8 Located in Mitochondrial Complex I in Different Diseases

et al. 2022

View full text Add to dashboard Cite

NADH:ubiquinone oxidoreductase core subunit S8 (NDUFS8) is an essential core subunit and component of the iron-sulfur (FeS) fragment of mitochondrial complex I directly involved in the electron transfer process and energy metabolism. Pathogenic variants of the NDUFS8 are relevant to infantile-onset and severe diseases, including Leigh syndrome, cancer, and diabetes mellitus. With over 1000 nuclear genes potentially causing a mitochondrial disorder, the current diagnostic approach requires targeted molecular analysis, guided by a combination of clinical and biochemical features. Currently, there are only several studies on pathogenic variants of the NDUFS8 in Leigh syndrome, and a lack of literature on its precise mechanism in cancer and diabetes mellitus exists. Therefore, NDUFS8-related diseases should be extensively explored and precisely diagnosed at the molecular level with the application of next-generation sequencing technologies. A more distinct comprehension will be needed to shed light on NDUFS8 and its related diseases for further research. In this review, a comprehensive summary of the current knowledge about NDUFS8 structural function, its pathogenic mutations in Leigh syndrome, as well as its underlying roles in cancer and diabetes mellitus is provided, offering potential pathogenesis, progress, and therapeutic target of different diseases. We also put forward some problems and solutions for the following investigations.

show abstract

Adherence to Sulfur Microbial Diet and Ovarian Cancer Survival: Evidence from a Prospective Cohort Study

Cui,

Gong,

Liu

et al. 2023

Molecular Nutrition Food Res

View full text Add to dashboard Cite

ScopeThe study aims to investigate the role of the sulfur microbial diet in the survival of ovarian cancer (OC).Methods and resultsA prospective cohort study is conducted with 703 patients diagnosed with OC between 2015 and 2020. Diet information is collected using a validated food frequency questionnaire. Deaths are ascertained up to March 31, 2021, via the death registry linkage. During the follow‐up period (median: 37.2 months, interquartile range: 24.7–50.2 months), 130 deaths are observed. A higher sulfur microbial diet score is significantly associated with an increased risk of all‐cause mortality among OC patients (tertile 3 vs tertile 1: HR = 1.93, 95% CI = 1.11–3.35). Each 1‐standard deviation increment in the sulfur microbial diet score increases the all‐cause mortality risk by 33% (95% CI = 1.04–1.71). Stratified analysis shows that significant associations are found in OC patients diagnosed over 50 years of age, with body mass index ≥24 kg m−2, who changed their diet after diagnosis, or without residual lesions.ConclusionsAdherence to the sulfur microbial diet, characterized by high intakes of red meats and processed meats, and low intakes of fruits, vegetables, and whole grains, is associated with poor survival in OC patients.

show abstract

Iron-sulphur cluster biogenesis factor LYRM4 is a novel prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma

Cited by 8 publications

References 62 publications

Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma

Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma

Emerging Roles of NDUFS8 Located in Mitochondrial Complex I in Different Diseases

Adherence to Sulfur Microbial Diet and Ovarian Cancer Survival: Evidence from a Prospective Cohort Study

Contact Info

Product

Resources

About