Low EIF2B5 expression predicts poor prognosis in ovarian cancer

Hou, Lin; Jiao, Yan; Li, Yanqing; Luo, Zhangping; Zhang, Xueying; Pan, Guoqiang; Zhao, Yongming; Yang, Zhaoying; He, Miao

doi:10.1097/md.0000000000018666

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…Our group has, after a long period of research, identified a variety of novel LC biomarkers [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. This study confirmed that hepatic PDK2 levels were lower in cancerous tissue than in normal tissue.…”

Section: Discussionmentioning

confidence: 54%

PDK2: a novel diagnostic and prognostic biomarker for liver cancer

Liu

Jiao

et al. 2020

Preprint

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Background: Liver cancer (LC) is a common malignancy with very high morbidity. Pyruvate dehydrogenase kinases (PDKs) are regulators of mitochondrial pyruvate dehydrogenase complexes (PDCs) and play an important role in regulating cellular energy metabolism. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PDK2 mRNA in LC, and to explore the value of PDK2 in the diagnosis and prognosis of LC.Methods: The TCGA database, containing the clinical data of 373 LC patients, includes information on PDK2 expression values. The receiver operating characteristic (ROC) curve of PDK2 was drawn to evaluate its diagnostic ability. Patients were divided into PDK2 high- and low-expressing groups by threshold levels. The Chi-square test was used to evaluate the correlation between PDK2 levels and clinicopathological characteristics. The Kaplan-Meier estimator and Cox regression analysis were performed to assess the effect of PDK2 levels on survival outcomes.Results: PDK2 expression in LC tissue was lower than that in normal liver tissues. According to the area under the curve (AUC) value calculated by ROC, PDK2 has a considerable diagnostic value for LC prognosis. The decreased expression of PDK2 is associated with clinical parameters, such as histologic grade ( P =0.0001), radiation therapy ( P =0.0490), vital status ( P =0.0240), and overall survival (OS) ( P =0.0222). Multivariate analysis shows that decreased PDK2 level is an independent risk factor for predicting poor prognosis in LC.Conclusions: PDK2 has a significant impact on the prognosis of LC and is a potential biomarker for the diagnosis and prognosis of LC.

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Section: Discussionmentioning

confidence: 54%

PDK2: a novel diagnostic and prognostic biomarker for liver cancer

Liu

Jiao

et al. 2020

Preprint

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“…Perhaps the most interesting finding is early research regarding EIF2B5 mainly aimed to study the roles of its expression in few cancerous tissue(Hou et al, 2020; Jiao et al, 2018; Xue et al, 2014; Yang et al, 2014), multiple sclerosis(Zahoor et al, 2017), and vanishing white matter (VWM) (Dietrich et al, 2005)syndrome. Importantly, the eIF2B complex plays a central role in the cellular integrated stress response (ISR).…”

Section: Discussionmentioning

confidence: 99%

Druggable causal genes of bipolar disorder identified through Mendelian Randomization analysis offer a route to intervention in integrated stress response

Ting

2023

Preprint

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Bipolar disorder (BD) is known to be comorbid with many medical and psychiatric conditions and they may share inflammatory and stress-related aetiologies, which could give rise to this association. Psychosomatic illnesses are characterized by widespread immune signaling in the central nervous system, oxidative stress, and increased immune trafficking into the brain. The integrated stress response (ISR) responds to a variety of different stress conditions that lead to alterations in cellular homeostasis. However, as a causative mechanism underlying the cognitive deficits and neurodegeneration in a broad range of brain disorders, the impact of ISR on BD is understudied, particularly for the ISR’s central regulatory switch lies in eIF2 ternary complex formation. We aimed to prioritize eIF2-associated genes for follow-up studies using the summary data-based Mendelian Randomization (SMR) and Bayesian colocalization (COLOC) methods to integrate the summary-level data of the GWAS on BD and the expression quantitative trait locus (eQTL) study in blood. We utilized the GWAS data including 41917 BD cases and 371549 controls from the Psychiatric Genomics Consortium and the eQTL data from 31,684 participants of predominantly European ancestry from the eQTLGen consortium. Plus, we use Graph DB to alt drug targets. The SMR analysis identified EIF2B5 gene that were associated with BD due to no linkage but pleiotropy or causality. The COLOC analysis strongly suggested that EIF2B5 and the trait of BD were affected by shared causal variants, and thus were colocalized. Utilizing data in EpiGraphDB we find other putative causal BD genes (EIF2AK4 and GSK3B) to prioritise potential alternative drug targets.

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“…Furthermore, depletion of EIF2B5 facilitated MYC-driven apoptosis of colorectal cancer SW480 cells (Schmidt et al 2019 ). Hou et al demonstrated that EIF2B5 was lowly expressed in OC tissues (Hou et al 2020 ). In this work, we also identified the downregulation of EIF2B5 in OC tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, dysregulated EIF2B5 expression was also corrected with the progression of liver cancer (Jiao et al 2018 ), colorectal cancer (Palaniappan et al 2016 ) and diffuse large B-cell lymphoma (Unterluggauer et al 2018 ). EIF2B5 was lowly expressed in OC tissues, implying its relevance with OC (Hou et al 2020 ). MethPrimer 2.0 predicted that there were CpG islands in EIF2B5 promoter region, suggesting that EIF2B5 methylation was increased.…”

Section: Introductionmentioning

confidence: 99%

LncRNA KCNQ1OT1 promotes the metastasis of ovarian cancer by increasing the methylation of EIF2B5 promoter

Chen

et al. 2022

Mol Med

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Background Long non-coding RNAs (lncRNAs) have emerged as regulators of human malignancies, including ovarian cancer (OC). LncRNA KCNQ1OT1 could promote OC progression, and EIF2B5 was associated with development of several tumors. This project was aimed to explore the role of lncRNA KCNQ1OT1 in OC development, as well as the involving action mechanism. Methods Reverse transcription quantitative polymerase chain reaction (RT-qPCR) or Western blotting was employed to determine the expression levels of KCNQ1OT1 and EIF2B5. OC cell proliferation was evaluated by MTT and colony formation assays, and wound healing and Transwell assays were implemented to monitor cell migration and invasion, respectively. The methylation status of EIF2B5 promoter was examined by MS-PCR, to clarify whether the expression of EIF2B5 was decreased. The binding activity of KCNQ1OT1 to methyltransferases DNMT1, DNMT3A and DNMT3B was determined by dual luciferase reporter assay or RIP assay, to explore the potential of KCNQ1OT1 alters the expression of its downstream gene. ChIP assay was carried out to verify the combination between EIF2B5 promoter and above three methyltransferases. Results Expression of lncRNA KCNQ1OT1 was increased in OC tissues and cells. EIF2B5 expression was downregulated in OC, which was inversely correlated with KCNQ1OT1. Knockdown of KCNQ1OT1 inhibited OC cell proliferation and metastasis. KCNQ1OT1 could downregulate EIF2B5 expression by recruiting DNA methyltransferases into EIF2B5 promoter. Furthermore, interference of EIF2B5 expression rescued KCNQ1OT1 depletion-induced inhibitory impact on OC cell proliferation and metastasis. Conclusion Our findings evidenced that lncRNA KCNQ1OT1 aggravated ovarian cancer metastasis by decreasing EIF2B5 expression level, and provided a novel therapeutic strategy for OC.

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Low EIF2B5 expression predicts poor prognosis in ovarian cancer

Cited by 8 publications

References 26 publications

PDK2: a novel diagnostic and prognostic biomarker for liver cancer

PDK2: a novel diagnostic and prognostic biomarker for liver cancer

Druggable causal genes of bipolar disorder identified through Mendelian Randomization analysis offer a route to intervention in integrated stress response

LncRNA KCNQ1OT1 promotes the metastasis of ovarian cancer by increasing the methylation of EIF2B5 promoter

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