Hypoxia-induced elevated NDRG1 mediates apoptosis through reprograming mitochondrial fission in HCC

Guo, Dongdong; Xie, Kunfeng; Luo, Xingjing

doi:10.1016/j.gene.2020.144552

Cited by 26 publications

(28 citation statements)

References 20 publications

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“…The cells were cultured in Dulbecco's modified Eagle's medium (DMEM) containing a combination of 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 mg/mL streptomycin at 37°C with 5% CO 2 . The cells were housed in a hypoxia workstation for 24 h with 1% O 2 [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR‐21‐5p/CASKIN1/cAMP Axis

Dong

Yuemaierabola

et al. 2021

Oxidative Medicine and Cellular Longevity

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Glioma is a type of malignant intracranial tumor. Extensive research has identified the participation of long noncoding RNAs (lncRNAs) in glioma progression. This study investigated the mechanism of LINC00294 in mitochondrial function and glioma cell apoptosis. Glioma miRNA and mRNA microarray datasets were obtained, and differentially expressed lncRNAs in glioma were screened through various databases. The LINC00294 expression in glioma patients and glioma cells was detected. Glioma cells were treated under hypoxic conditions and transfected with LINC00294 silencing. The apoptosis and mitochondrial function of glioma cells were measured. The expressions of and relations among miR-21-5p, CASKIN1, and cAMP in glioma cells were analyzed. Under hypoxic conditions and LINC00294 silencing, the apoptosis and mitochondrial function of glioma cells were detected after inhibiting miR-21-5p or overexpressing CASKIN1. Our results indicated that LINC00294 was downregulated in glioma. LINC00294 silencing inhibited glioma cell apoptosis under hypoxia. LINC00294 silencing reversed the inhibition of hypoxia on mitochondrial function under hypoxia. LINC00294 promoted the CASKIN1 expression by sponging miR-21-5p and activated the cAMP pathway. Inhibition of miR-21-5p or overexpression of CASKIN1 annulled the effects of LINC00294 silencing on mitochondrial function and glioma cell apoptosis under hypoxia. In conclusion, LINC00294 elevated the CASKIN1 expression by sponging miR-21-5p and activating the cAMP signaling pathway, thus inhibiting mitochondrial function and facilitating glioma cell apoptosis.

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Section: Methodsmentioning

confidence: 99%

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR‐21‐5p/CASKIN1/cAMP Axis

Dong

Yuemaierabola

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…It can inhibit ferroptosis in HCC through reducing cytochrome P450 oxidoreductase [ 39 ]. Hypoxia-mediated NDRG1 upregulation modulates apoptotic levels via driving mitochondrial fission in HCC [ 40 ]. NDRG1 acts as a predictor of metastases, relapse, and undesirable prognosis in HCC [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

A Cell Cycle Progression-Derived Gene Signature to Predict Prognosis and Therapeutic Response in Hepatocellular Carcinoma

et al. 2021

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Objective. Dysregulation of cell cycle progression (CCP) is one of the hallmarks of cancer. Here, our study is aimed at developing a CCP-derived gene signature for predicting high-risk population of hepatocellular carcinoma (HCC). Methods. Our study retrospectively analyzed the transcriptome profiling and clinical information of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects. Uni- and multivariate cox regression models were conducted for identifying which hallmarks of cancer were risk factors of HCC. CCP-derived gene signature was developed with LASSO method. The predictive efficacy was verified by ROC curves and subgroup analyses. A nomogram was then generated and validated by ROC, calibration, and decisive curves. Immune cell infiltration was estimated with ssGSEA method. Potential small molecular compounds were predicted via CTRP and CMap analyses. The response to chemotherapeutic agents was evaluated based on the GDSC project. Results. Among hallmarks of cancer, CCP was identified as a dominant risk factor for HCC prognosis. CCP-derived gene signature displayed the favorable predictive efficacy in HCC prognosis independent of other clinicopathological parameters. A nomogram was generated for optimizing risk stratification and quantifying risk evaluation. CCP-derived signature was in relation to immune cell infiltration, HLA, and immune checkpoint expression. Combining CTRP and CMap analyses, fluvastatin was identified as a promising therapeutic agent against HCC. Furthermore, CCP-derived signature might be applied for predicting the response to doxorubicin and gemcitabine. Conclusion. Collectively, CCP-derived gene signature was a promising marker in prediction of survival outcomes and therapeutic responses for HCC patients.

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“…N-myc downregulated 1 (NDRG1) was a tumor suppressor, which has been reported in various studies; it could attenuate NF-kB and TGF-b pathways in pancreatic cancer cells, and downregulated NDRG1 was related to increased proliferation, invasion, and migration of digestive cancers [ 30 – 33 ]. It additionally involves apoptosis, glycolytic, and lipid metabolism in cancer cells, and virus infection process was also related to NDRG1 [ 34 – 40 ]. Another signature, mitogen-activated protein kinase 2 (MAP4K2), was involved in MAPK signaling pathway, which corroborated with the enrichment results.…”

Section: Discussionmentioning

confidence: 99%

Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients

Liu

Chen

2021

Journal of Oncology

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Background. Hepatocellular carcinoma (HCC) is the leading liver cancer with special immune microenvironment, which played vital roles in tumor relapse and poor drug responses. In this study, we aimed to explore the prognostic immune signatures in HCC and tried to construct an immune-risk model for patient evaluation. Methods. RNA sequencing profiles of HCC patients were collected from the cancer genome Atlas (TCGA), international cancer genome consortium (ICGC), and gene expression omnibus (GEO) databases (GSE14520). Differentially expressed immune genes, derived from ImmPort database and MSigDB signaling pathway lists, between tumor and normal tissues were analyzed with Limma package in R environment. Univariate Cox regression was performed to find survival-related immune genes in TCGA dataset, and in further random forest algorithm analysis, significantly changed immune genes were used to generate a multivariate Cox model to calculate the corresponding immune-risk score. The model was examined in the other two datasets with recipient operation curve (ROC) and survival analysis. Risk effects of immune-risk score and clinical characteristics of patients were individually evaluated, and significant factors were then used to generate a nomogram. Results. There were 52 downregulated and 259 upregulated immune genes between tumor and relatively normal tissues, and the final immune-risk model (based on SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV and MAP4K2) can better differentiate patients into high and low immune-risk subpopulations, in which high score patients showed worse outcomes after resection ( p < 0.05 ). The differentially enriched pathways between the two groups were mainly about cell proliferation and cytokine production, and calculated immune-risk score was also highly correlated with immune infiltration levels. The nomogram, constructed with immune-risk score and tumor stages, showed high accuracy and clinical benefits in prediction of 1-, 3- and 5-year overall survival, which is useful in clinical practice. Conclusion. The immune-risk model, based on expression of SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV, and MAP4K2, can better differentiate patients into high and low immune-risk groups. Combined nomogram, using immune-risk score and tumor stages, could make accurate prediction of 1-, 3- and 5-year survival in HCC patients.

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Hypoxia-induced elevated NDRG1 mediates apoptosis through reprograming mitochondrial fission in HCC

Cited by 26 publications

References 20 publications

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR‐21‐5p/CASKIN1/cAMP Axis

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR‐21‐5p/CASKIN1/cAMP Axis

A Cell Cycle Progression-Derived Gene Signature to Predict Prognosis and Therapeutic Response in Hepatocellular Carcinoma

Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients

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