Immune-related DNA methylation signature associated with APLN expression predicts prognostic of hepatocellular carcinoma

Tian, Fei; HU, HUAN; WANG, DI; Ding, Huan; Chi, Qingjia; LIANG, HUAPING; ZENG, WENLI

doi:10.32604/biocell.2022.020198

Cited by 6 publications

(3 citation statements)

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“…Furthermore, immune infiltration analysis shows a correlation between target genes and several immune cells ( Tian et al, 2022 ). We revealed that 4 target genes are significantly related to CD4 + memory static T cells.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatical and in vitro study on drug targets for liver cirrhosis based on unsupervised consensus clustering and immune cell infiltration

et al. 2023

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Liver cirrhosis is one of the most common cause of death in the world. The progress of liver cirrhosis involves health, liver cirrhosis and liver cancer, leading to great challenges in the diagnosis of the disease. Drug targets, which could be obtained conveniently, can help clinicians improve prognosis and treatment. Liver cirrhosis is associated with serum calcium levels. And studies reported Tanshinone IIA plays a therapeutic role in liver injury through activating calcium-dependent apoptosis. In this study, we explored the diagnostic key targets of Tanshinone IIA in liver cirrhosis through exploration of comprehensive dataset including health, liver cirrhosis and liver cancer patients. The unsupervised consensus clustering algorithm identified 3 novel subtypes in which differentially expressed genes (DEGs) between both subtypes were found by pairwise comparison. Then, 4 key drug targets of Tanshinone IIA were determined through the intersection of these DEGs. The diagnostic performance of target genes was assessed and further verified in the external dataset. We found that the 4 key drug targets could be used as effective diagnostic biomarkers. Then the immune scores in the high and low expression groups of target genes were estimated to identify significantly expressed immune cells. In addition, the immune infiltration of high and low target gene expression groups in several immune cells were significantly different. The findings suggest that 4 key drug targets may be a simple and useful diagnostic tool for predicting patients with cirrhosis. We further studied the carcinogenesis role of AKR1C3 and TPX2 in vitro. Both mRNA and protein expression in hepatoma carcinoma cells was detected using qRT-PCR and Western blot. And the knockdown of AKR1C3 and TPX2 significantly suppressed cell proliferation, migration and invasion.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatical and in vitro study on drug targets for liver cirrhosis based on unsupervised consensus clustering and immune cell infiltration

et al. 2023

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“…By detecting lactate and glycolysis related indexes in A549 cells, Our results suggest that FGS treatment can inhibiting the glycolytic pathway to significantly inhibit the growth of tumors. Since the link of higher expression levels of GLUTs and certain other enzymes essential in glycolysis, such as LDHA and PFK-B, has been established with tumor growth in various studies, [34][35][36][37] we investigated the significance of LDHA, GLUT1, and PKM2. The analysis of data for healthy individuals and lung cancer patients in the TCGA database presented LDHA, GLUT1, and PKM2 as typical oncogenes; literature has reported that inhibiting the expression of these enzymes effectively suppresses tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Natural product fargesin interferes with H3 histone lactylation via targeting PKM2 to inhibit non‐small cell lung cancer tumorigenesis

Guo,

Tang,

Wang

et al. 2023

BioFactors

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Non‐small cell lung cancer (NSCLC) is one of the most common malignant tumors. There is an urgent need to find more effective drugs that inhibit NSCLC. Fargesin (FGS) has demonstrated anti‐tumor effects; however, its efficacy and the molecular mechanism of inhibiting NSCLC are unclear. Herein, we investigated FGS’ inhibitory effects on NSCLC by CCK8 and EdU assays and cell cycle analysis of A549 cells in vitro and in a nude mouse tumor transplantation model in vivo. FGS (10–50 μM) significantly inhibited cell proliferation and down‐regulated expression levels of CDK1 and CCND1. Transcriptomic analysis showed that FGS regulated the cell metabolic process pathway. Differential metabolites with FGS treatment were enriched in glycolysis and pyruvate pathways. Cell metabolism assay were used to evaluate the oxygen consumption rate (OCR), Extracellular acidification rate (ECAR) in A549 cells. FGS also inhibited the production of cellular lactate and the expression of LDHA, LDHB, PKM2, and SLC2A1. These genes were identified as important oncogenes in lung cancer, and their binding to FGS was confirmed by molecular docking simulation. Notably, the over‐expression and gene silencing experiments signified PKM2 as the molecular target of FGS for anti‐tumorigenesis. Moreover, the H3 histone lactylation, were correlated with tumorigenesis, were inhibited with FGS treatment. Conclusively, FGS inhibited the aerobic glycolytic and H3 histone lactylation signaling pathways in A549 NSCLC cells by targeting PKM2. These findings provide evidence of the therapeutic potential of FGS in NSCLC.

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“…These mechanisms help to explain the specific loss of RARRES3 in basal-like tumors. Promoter methylation is an important mechanism of gene downregulation (Tian et al, 2022). Via in-silico analysis using data from TCGA-BRCA, we found that RARRES3 might be epigenetically silenced by promoter hypermethylation in basal-like breast tumors.…”

Section: Tablementioning

confidence: 91%

Methyltransferase 3A-mediated promoter methylation represses retinoic acid receptor responder 3 expression in basal-like breast cancer

Tuo¹,

LIU²

2023

Biocell

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Retinoic acid receptor responder 3 (RARRES3) has been characterized as a tumor suppressor in multiple types of cancer. This study aimed to examine the expression profile of RARRES3 across the PAM50 subtypes of breast cancer. The DNA methylation status of RARRES3 was checked in the basal-like subtype, and the underlying mechanisms of its dysregulation were explored. RNA-sequencing (seq) and methylation data from The Cancer Genome Atlas were used for in-silico analysis. Basal-like representative SUM149 and MDA-MB-468 cell lines were used for in vitro and in vivo studies.Compared to tumor-adjacent normal tissues, only the basal-like tumor tissues had significantly downregulated RARRES3 expression. The methylation level of four CpG sites in the promoter region showed a strong negative correlation with RARRES3 expression. The gene coding for DNA methyltransferase 3A (DNMT3A) had consistent positive correlations with the methylation of the CpG sites. Chromatin Immunoprecipitation-quantitative polymerase chain-reaction and bisulfite sequencing PCR showed that DNMT3A could bind to the promoter region of RARRES3 and promote methylation of the CpG sites within the region. DNMT3A knockdown significantly restored RARRES3 expression at the mRNA and protein level in the two cell lines. CCK-8, colony formation, and flow cytometric analysis showed that RARRES3 overexpression attenuated the growth-promoting effects of DNMT3A overexpression and also weakened the DNMT3A overexpression-induced activation of ERK1/2 and PI3K/AKT signaling. In summary, this study revealed that DNMT3A enhances promoter methylation of the RARRES3 gene and suppresses its transcription in basal-like breast cancer. The DNMT3A-RARRES3 signaling pathway might be a potential target for the treatment of this tumor subtype.

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Immune-related DNA methylation signature associated with APLN expression predicts prognostic of hepatocellular carcinoma

Cited by 6 publications

References 58 publications

Integrated bioinformatical and in vitro study on drug targets for liver cirrhosis based on unsupervised consensus clustering and immune cell infiltration

Integrated bioinformatical and in vitro study on drug targets for liver cirrhosis based on unsupervised consensus clustering and immune cell infiltration

Natural product fargesin interferes with H3 histone lactylation via targeting PKM2 to inhibit non‐small cell lung cancer tumorigenesis

Methyltransferase 3A-mediated promoter methylation represses retinoic acid receptor responder 3 expression in basal-like breast cancer

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