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Increasingly advanced biology technique has revealed that long non-coding RNAs (lncRNA) as critical factors that exert significant regulatory effects on biological functions by modulating gene transcription, epigenetic modifications and protein translation. A newly emerging lncRNA, ladybird homeobox 2 (LBX2)-antisense RNA 1 (LBX2-AS1), was found to be highly expressed in various tumors. Moreover, it is functionally linked to the regulation of essential tumor-related biological processes, such as cell proliferation and apoptosis, through interactions with multiple signaling molecules/pathways. The important roles played by LBX2-AS1 in cancer initiation and progression suggest that this lncRNA has enormous clinical potential for use as a novel biomarker or therapeutic target. In this article, we retrospectively review the latest advances in research exploring the roles of the lncRNA LBX2-AS1 in oncology field, highlighting its involvement in a comprehensive network of molecular mechanisms underlying diverse cancers and examining its potential applications in clinical practice.

Qingfei Chu,&ast; Xinyu Gu,&ast; Qiuxian Zheng, Jing Wang, Haihong Zhu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong Zhu Tel +86-13656632056Email zhuhh72@zju.edu.cnBackground: PPAT (phosphoribosyl pyrophosphate amido transferase) catalyzes the first committed step of de novo purine biosynthesis and is a key regulatory point in the biosynthesis of nascent purine nucleotides. However, the clinical significance and biologic role of PPAT in hepatocellular carcinoma (HCC) remain unknown.Methods: We compared the expression of PPAT in carcinomatous and precancerous hepatocellular carcinoma tissues by immunohistochemistry in 90 cases of HCC. Correlation analysis was also made on clinical data, survival, classification, and staging.Results: The expression of PPAT in HCC tumor tissues is significantly higher than that in adjacent normal tissues. The results of the Kaplan–Meier analysis showed that HCC patients with high PPAT expression survived shorter than those with low PPAT expression. Moreover, the expression of PPAT was significantly associated with the tumor grade (P=0.014), PD-L1 (P< 0.001), and CTLA4 (P=0.003). The later grade of the tumor, the higher the expression of PPAT. In the PD-L1 high expression group, PPAT is also highly expressed.Conclusion: Our study demonstrated that PPAT expression might be included in the process of carcinogenesis and prognosis. Hence, PPAT could be served as a new prognostic biomarker for patients of HCC.Keywords: PPAT, HCC, prognosis, biomarker, metabolism

Recently, long noncoding RNAs (lncRNAs) have attracted great attention from researchers. LncRNAs are non-protein-coding RNAs of more than 200 nucleotides in length. Multiple studies have been published on the relationship between lncRNA expression and the progression of human diseases. LncRNA small nucleolar RNA host gene 4 (SNHG4), a member of the lncRNA SNHG family, is abnormally expressed in a variety of human diseases, including gastric cancer, renal cell carcinoma, glioblastoma, neuroblastoma, prostate cancer, colorectal cancer, osteosarcoma, cervical cancer, liver cancer, lung cancer, non-small-cell lung cancer, neonatal pneumonia, diabetic retinopathy, neuropathic pain, acute cerebral infarction, acute myeloid leukaemia, and endometriosis. In this paper, the structure of SNHG4 is first introduced, and then studies in humans, animal models and cells are summarized to highlight the expression and function of SNHG4 in the above diseases. In addition, the specific mechanism of SNHG4 as a competing endogenous RNA (ceRNA) is discussed. The findings indicate that SNHG4 can be used as a biomarker for disease prognosis evaluation and as a potential target for disease diagnosis and treatment.

Long noncoding RNAs (lncRNAs) are involved in multiple functions such as the regulation of cellular homeostasis. They play prominent roles in the pathogenesis of human cancer, and contribute to every hallmark of cancer. The novel cancer-related lncRNA DLX6 antisense RNA 1 (DLX6-AS1) plays an essential regulatory role in enhancing and initiating carcinogenesis and tumor progression. This progression is due to the aberrant regulation of downstream factors in vitro as well as in vivo. DLX6-AS1 is significantly dysregulated in various cancers. DLX6-AS1 functions in tumor initiation and progression are regulated at the epigenetic, transcription, and posttranscriptional regulation levels. DLX6-AS1 functions as an oncogene, binding to miRNA targeting sites competing endogenous RNAs and causing the upregulation of downstream tumor-related genes and carcinogenesis. The regulation and detailed molecular mechanisms of DLX6-AS1 and its potential role in malignancies are comprehensively described in this paper. DLX6-AS1 has the potential to become a novel biomarker and therapeutic target for cancer.

Background: Recent studies have shown that the transcription factor E2F4 is involved in the progression of various tumors, but its expression and influence on immune cell infiltration and biological functions are largely unknown in hepatocellular carcinoma (HCC). Methods: The Cancer Genome Atlas (TCGA) database, the Tumor Immune Estimation Resource (TIMER) and related online tools as well as a tissue microarray (TMA) were used for analyses in our study. Results: E2F4 expression was elevated in HCC tumor tissue compared with adjacent normal tissue at both the mRNA and protein levels. Overexpression of E2F4 was markedly related to a poor prognosis in HCC patients. In addition, positively and negatively correlated significant genes of E2F4 were identified in HCC. Pathway enrichment analyses revealed that the top 100 positively correlated significant genes of E2F4 were closely related to nuclear splicing and degradation-related pathways. Furthermore, nine hub genes correlated with E2F4 expression were validated based on a protein-protein interaction (PPI) network. It was also demonstrated that E2F4 expression was negatively correlated to immune purity and positively correlated to immune cell infiltration. Conclusion: E2F4 could serve as a novel biomarker for HCC diagnosis and prognosis prediction.

Background: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. Methods: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. Results: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=−1.06, range between −1.55 and −0.57, WMD=−40.39, range between −80.20 and −0.48, and WMD=−55.26, range between −105.92 and −4.60, respectively). Conclusions: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.

MicroRNAs (miRNAs) are one type of noncoding RNAs that interfere with mRNA translation to downregulate gene expression, which results in posttranscriptional gene silencing. Over the past two decades, miRNAs have been widely reported to impact the progression of malignant tumours by interfering with cancer initiation and progression; therefore, miRNAs represent potential new diagnostic and therapeutic tools. miR-650 is a newly identified miR, and increasing studies have demonstrated that miR-650 plays critical roles in cancer progression, such as mediating the Wnt signalling pathway/AXIN1 (axis inhibition protein 1) axis in hepatocellular carcinoma. Nevertheless, associations between the expression patterns and molecular mechanisms of miR-650 in cancer have not been comprehensively described. In this article, we review the existing evidence regarding the mechanisms by which miR-650 expression is altered and their relation to cancer. Moreover, the promising clinical application of miR-650 for diagnosis and treatment is highlighted.

Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes. Epigenetic modifications regulate many biological processes, such as growth, aging, and various diseases, including cancer. With the advancement of next-generation sequencing technology, the role of RNA modifications in cancer progression has become increasingly prominent and is a hot spot in scientific research. This review studied several common RNA modifications, such as N

Nonalcoholic fatty liver disease (NAFLD) is a class of metabolic-associated liver diseases. Aberrant lipid consumption plays an important role in NAFLD pathogenesis. It has been shown CD1d can bind to multiple different lysophospholipids and associated with NAFLD progression. However, the mechanism of CD1d regulation in NAFLD is not completely understood. In this study, we established a NAFLD mouse model by feeding C57/BL6J mice a high-fat diet (HFD) for 24 weeks. Subsequently, we performed integrated transcriptomics and metabolomics analyses to thoroughly probe the role of CD1d in NAFLD progression. In the present study, we demonstrate that CD1d expression was significantly decreased in our murine model of NAFLD. Additionally, we show CD1d knockdown (CD1d KO) in HFD-fed wild-type (WT) mice induced NAFLD, which resulted in weight gain, exaggerated liver injury, and hepatic steatosis. We uncover the crucial roles of CD1d deficiency results in accumulated lipid accumulation. We further explored the CD1d deficiency in NAFLD regarding the transcriptional landscapes, microbiota environment, metabolomics change, and transcriptomics differences. In conclusion, our data demonstrate CD1d plays an important role in NAFLD pathogenesis and may represent a potential therapeutic target for the further therapy.

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

Background: 5-Methylcytosine (m5C) plays essential roles in hepatocellular carcinoma (HCC), but the association between m5C regulation and immune cell infiltration in HCC has not yet been clarified.Methods: In this study, we analysed 371 patients with HCC from The Cancer Genome Atlas (TCGA) database, and the expression of 13 m5C regulators was investigated. Additionally, gene set variation analysis (GSVA), unsupervised clustering analysis, single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and immunohistochemical (IHC) staining were performed.Results: Among the 371 patients, 41 had mutations in m5C regulators, the frequency of which was 11.26%. Compared with normal hepatic tissues, the expression of m5C regulators with copy number variations (CNVs) expansion was significantly higher than that in HCC tissues. Then, we identified three m5C modification patterns that had obvious tumour microenvironment (TME) cell infiltration characteristics. The prognostic analysis of the three major m5C modification subtypes showed that Cluster-2 had a clear survival advantage over the others. In addition, we found that DNMT1 was highly expressed in tumour tissues compared with normal tissues in a tissue microarray (TMA) and that it was positively correlated with many TME-infiltrating immune cells. High expression of the m5C regulator DNMT1 was related to a poor prognosis in patients with HCC. Furthermore, we developed three distinct Immu-clusters. Importantly, mRNAs related to the transcription of growth factor β (TGF-β)/EMT pathway were significantly up-regulated in Immu-cluster 2, indicating that this cluster is considered to be the immune rejection phenotype. Immu-cluster 3 showed elevated expression of mRNAs related to immune checkpoint genes.Conclusion: Our work revealed the association between m5C modification and immune regulators in the TME. These findings also suggest that DNMT1 has great potential as a prognostic biomarker and therapeutic target for HCC.

Background Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described. Methods HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices. Results Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells. Conclusions The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.

Background: 5-Methylcytosine (m5C) plays essential roles in hepatocellular carcinoma (HCC), but the association between m5C regulation and immune cell infiltration in HCC has not yet been clarified.Methods: In this study, we analysed 371 patients with HCC from The Cancer Genome Atlas (TCGA) database, and the expression of 13 m5C regulators was investigated. Additionally, gene set variation analysis (GSVA), unsupervised clustering analysis, single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and immunohistochemical (IHC) staining were performed.Results: Among the 371 patients, 41 had mutations in m5C regulators, the frequency of which was 11.26%. Then, we identified three m5C modification patterns that had obvious tumour microenvironment (TME) cell infiltration characteristics. Cluster-1 had an immune rejection phenotype; Cluster-2 had an immunoinflammatory phenotype; and Cluster-3 had an immune desert phenotype. In addition, we found that DNMT1 was highly expressed in tumour tissues compared with normal tissues in a tissue microarray (TMA) and that it was positively correlated with many TME-infiltrating immune cells. High expression of the m5C regulator DNMT1 was related to a poor prognosis in patients with HCC. Furthermore, we developed three Immu-clusters that were consistent with the immune characteristics of the m5C methylation modification patterns. We also discovered differences in the levels of immune cells and expression of chemokines and cytokines among the three Immu-clusters.Conclusions: Our work revealed the association between m5C modification and immune regulators in the TME. These findings also suggest that DNMT1 has great potential as a prognostic biomarker and therapeutic target for HCC.

Long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of multiple human cancers. An accumulating body of researches have investigated thymopoietin antisense RNA 1 (TMPO-AS1) as a newly discovered lncRNA, which functions as an oncogenic lncRNA that is upregulated in various human malignancies and associated with poor prognosis. Many studies have detected abnormally high expression levels of TMPO-AS1 in multiple cancers, such as lung cancer, breast cancer, colorectal cancer (CRC), hepatocellular carcinoma, CRC, gastric cancer, ovarian cancer, thyroid cancer, esophageal cancer, Wilms tumor, cervical cancer, retinoblastoma, bladder cancer, osteosarcoma, and prostate cancer. TMPO-AS1 has been subsequently demonstrated to play a pivotal role in tumorigenesis and progression. The aberrantly expressed TMPO-AS1 acts as a competing endogenous RNA (ceRNA) that inhibits miRNA expression, thus activating the expression of downstream oncogenes. This study comprehensively summarizes the aberrant expressions of TMPO-AS1 as reported in the current literature and explains the relevant biological regulation mechanisms in carcinogenesis and tumor progression. Corresponding studies have indicated that TMPO-AS1 has a potential value as a promising biomarker or a target for cancer therapy.

The long noncoding RNAs (lncRNAs) are non-coding RNAs that are more than 200 nucleotides in length, and one of several types of non-coding RNAs (ncRNAs). The lncRNAs function in diverse biological processes in normal cells, such as cellular differentiation and cell cycle regulation. There is also evidence that some aberrantly regulated lncRNAs function as oncogenes or tumor suppressor genes in various cancers. For example, TTN-AS1 is a lncRNA that binds to titin mRNA (TTN) and has pro-oncogenic effects in many cancers. Overexpression of TTN-AS1 correlates with poor prognosis in breast cancer, lung cancer, digestive system neoplasms, reproductive system cancers, and other cancers. Furthermore, increased TTN-AS1 expression correlates with more advanced pathology and tumor malignancy. In this review, we comprehensively summarize recent studies on the molecular mechanisms of TTN-AS1 regulation and the role of TTN-AS1 in the carcinogenesis and progression of numerous tumors.

Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis and progression. LncRNAs can participate in various biological processes, such as cell growth, anti-apoptosis functions, migration, and invasion. Cancer susceptibility candidate 15 (CASC15) is a cancer-related lncRNA that has been reported to play opposite roles in the pathogenesis of different types of cancers. Studies have shown that CASC15 is downregulated in ovarian cancer and neuroblastoma, acting mainly as a tumour suppressor, while it is highly expressed and carcinogenic in hepatocellular carcinoma (HCC), lung cancer, tongue squamous cell carcinoma, gastric cancer, colorectal cancer, cervical cancer, and breast cancer. Furthermore, aberrant CASC15 expression is associated with tumorigenesis, progression, and patient outcomes via regulation of target genes and signalling pathways. In this review, we summarize current data concerning the regulatory functions and underlying mechanisms of CASC15 in tumour development. We also highlight its potential clinical utility as a biomarker for early detection or as a therapeutic target in human cancers.

Background Although the tumour immune microenvironment is known to significantly influence immunotherapy outcomes, its association with changes in gene expression patterns in hepatocellular carcinoma (HCC) during immunotherapy and its effect on prognosis have not been clarified. Methods A total of 365 HCC samples from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset were stratified into training datasets and verification datasets. In the training datasets, immune-related genes were analysed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO)-Cox analyses to build a prognostic model. The TCGA-LIHC, GSE14520, and Imvigor210 cohorts were subjected to time-dependent receiver operating characteristic (ROC) and Kaplan–Meier survival curve analyses to verify the reliability of the developed model. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to study the underlying molecular mechanisms. Results Five immune-related genes (LDHA, PPAT, BFSP1, NR0B1, and PFKFB4) were identified and used to establish the prognostic model for patient response to HCC treatment. ROC curve analysis of the TCGA (training and validation sets) and GSE14520 cohorts confirmed the predictive ability of the five-gene-based model (AUC > 0.6). In addition, ROC and Kaplan–Meier analyses indicated that the model could stratify patients into a low-risk and a high-risk group, wherein the high-risk group exhibited worse prognosis and was less sensitive to immunotherapy than the low-risk group. Functional enrichment analysis predicted potential associations of the five genes with several metabolic processes and oncological signatures. Conclusions We established a novel five-gene-based prognostic model based on the tumour immune microenvironment that can predict immunotherapy efficacy in HCC patients.

Additional file 5: Table S2. The sample information of TCGA training set and validation set.

Long non-coding RNAs (lncRNAs) regulate gene expression and carcinogenesis. The lncRNA heart and neural crest derivatives expressed transcript 2 antisense RNA 1 (HAND2‑AS1) suppresses tumor growth, and its expression level was lower in tumor tissues than in adjacent normal tissues of most types of human cancers, including non-small cell lung cancer, ovarian cancer, breast cancer, gastric cancer, colorectal cancer, cervical cancer, endometrial cancer, prostate cancer, and esophagus squamous cell carcinoma. However, one study reported that the HAND2‑AS1 expression was upregulated in hepatocellular carcinoma tissues comparing with non-tumor tissues and it promoted tumor development. The aberrant expression of HAND2-AS1 was strongly linked to tumor progression and prognosis. Moreover, HAND2-AS1 was involved in tumor cell proliferation, differentiation, apoptosis, and cellular glucose metabolism. This review summarizes data on the expression profile, functions, underlying mechanism, and clinical value of HAND2-AS1 in cancer. The expression profile of HAND2-AS1 in 33 tumors was evaluated by bioinformatics analysis of The Cancer Genome Atlas.

Cancer remains the second leading life-threatening disease worldwide. Increasing evidence indicates that long non-coding RNAs (lncRNAs) play an important role in multiple physiological and pathological processes, including gene amplification, mutation, rearrangement, and overexpression regulations. In this review, we comprehensively summarize the current knowledge of lncRNA AGAP2-AS1 from a cancer perspective. As a member of the lncRNA family, lncRNA AGAP2-AS1 is upregulated in solid tumor malignancies, functions as an oncogene, and plays a key role in tumorigenesis and tumor progression. AGAP2-AS1 expression is significantly increased in clinical cancer tissue samples, cell lines, and in vivo, and is closely related to an unfavorable prognosis in several cancers. Upregulated lncRNA AGAP2-AS1 binds with microRNAs (miRNAs) and promotes activation of downstream genes. This aberrant regulation induces carcinogenesis and tumorigenesis. Here we provide a comprehensive overview of AGAP2-AS1 in cancer progression that leads to an improved understanding of the effects of AGAP2-AS1 on early detection and therapeutic approaches. This information is essential for the future development of lncRNA AGAP2-AS1 as a potential therapy against these devastating cancers.

Background and objective: Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/d-galactosamine (d-GaIN) in mice. Methods: Male C57BL/6 mice were given LPS and d-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively. Results: A mouse model of ALF can be constructed successfully using LPS/d-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/d-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition. Conclusions: In LPS/d-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.

Metabolic reprogramming is a hallmark of tumors, including hepatocellular carcinoma (HCC). We used data from The Cancer Genome Atlas and the International Cancer Genome Consortium to assess the alterations in glycolytic and cholesterogenic genes in HCC and to determine their association with clinical features in HCC patients. Based on the gene expression profiles from these databases, we established four subtypes of HCC: cholesterogenic, glycolytic, mixed, and quiescent. The prognosis of the cholesterogenic subgroup was poorer than that of the glycolytic group. Tumors in the glycolytic group were more sensitive to chemotherapy. We also explored the relationships between these metabolic subtypes and previously established HCC subgroups. Glycolytic gene expression correlated strongly with poorer prognostic gene expression in the Hoshida classification of HCC. Whole-genome analyses indicated that aberrant amplification of TP53 and MYC in HCC were associated with abnormal anabolic cholesterol metabolism. The mRNA levels of mitochondrial pyruvate carriers 1 and 2 differed among the HCC metabolic subtypes. In a bioinformatics analysis we identified genomic characteristics of tumor metabolism that varied among different cancer types. These findings demonstrate that metabolic subtypes may be valuable prognostic indicators in HCC patients.

OBJECTIVE: To summarize the structure, regulatory mechanism, and target genes of hypoxia-inducible factor-1 alpha (HIF-1α) and to comprehensively expound its role in various chronic liver diseases, thus providing a new perspective on the treatment of various liver diseases. BACKGROUND: Liver disease, especially chronic liver disease, is a long-standing public health problem; the mortality rate due to end-stage cirrhosis and liver cancer is high worldwide and continues to grow. Moreover, there is a lack of effective targeted therapy for most liver diseases, such as fatty liver, alcoholic liver disease (ALD), and advanced liver cancer, for which drug treatment approaches are extremely limited. As the liver is a highly aerobic organ, an insufficient oxygen supply can induce a series of diseases, and HIF proteins play an important role in these processes. METHODS: Literature on HIF-1α and its effects on various liver diseases were extensively searched, and the feasibility and challenges of targeting HIF-1α to treat various chronic liver diseases were analyzed. CONCLUSIONS: HIF-1α is widely involved in the occurrence, development, and prognosis of ALD, nonalcoholic fatty liver disease (NAFLD), acetaminophen (APAP)-induced liver injury (AILI), viral hepatitis, hepatocellular carcinoma (HCC), and other liver diseases. HIF-1α participates in complex signaling pathways, and its expression is regulated in many liver diseases. These results suggest the feasibility and clinical significance of targeting HIF-1α to treat liver diseases.