scholarly journals RNA-seq Explores the Mechanism of Oxygen-Boosted Sonodynamic Therapy Based on All-in-One Nanobubbles to Enhance Ferroptosis for the Treatment of HCC

2021 ◽  
Author(s):  
Yichi Chen ◽  
Haitao Shang ◽  
Chunyue Wang ◽  
Jiaqi Zeng ◽  
Shentao Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Target Genes ◽  
Immune Cell ◽  
Low Frequency ◽  
Rna Seq ◽  
Sonodynamic Therapy ◽  
Kegg Pathways ◽  
Prognostic Analysis ◽  
Before And After

Abstract Background The combination of sonodynamic therapy and oxygenation strategy is widely used in cancer treatment. However, due to the complexity, heterogeneity and irreversible hypoxic environment produced by Hepatocellular carcinoma (HCC) tissues, oxygen-enhancing sonodynamic therapy (SDT) have failed to achieve the desired results. With the emergence of ferroptosis with reactive oxygen species (ROS) cytotoxicity, this novel cell death method has attracted widespread attention. Methods In this study, nanobubbles (NBs) were connected with the sonosensitizer Indocyanine green (ICG) to construct a 2-in-1 nanoplatform loaded with RAS-selective lethal (RSL3, ferroptosis promoter) (RSL3@O2-ICG NBs), combined with oxygen-enhanced SDT and potent ferroptosis. In addition, nanobubbles (NBs) combined with low-frequency ultrasound (LFUS) are called ultrasound-targeted nanobubble destruction (UTND) to ensure specific drug release and improve safety. Results MDA/GSH and other related experimental results show that RSL3@O2-ICG NBs can enhance SDT and ferroptosis. Through RNA sequencing (RNA-seq), the differential expression of LncRNA and mRNA before and after synergistic treatment was identified, and then GO and KEGG pathways were used to enrich and analyze target genes and pathways related ferroptosis sensitivity. Then we searched for the expression of differentially expressed genes in the TCGA Hepatocellular carcinoma cohort. At the same time, we evaluated the proportion of immune cell infiltration and the identification of co-expression network modules and related prognostic analysis. We found that it was significantly related to the tumor microenvironment of hepatocellular carcinoma. The prognostic risk genes "SLC37A2" and "ITGB7" may represent new hepatocellular carcinoma ferroptosis-inducing markers and have guiding significance for treating hepatocellular carcinoma. Conclusions The therapeutic effect of the in vitro synergistic treatment has been proven to be significant, revealing the prospect of 2-in-1 nanobubbles combined with SDT and ferroptosis in treating HCC.

scholarly journals OP0286 PROTEOMICS AND RNA SEQUENCING APPROACHES HIGHLIGHT THE ROLE OF ENDOTHELIAL CELL DYSREGULATION IN IL-1 AND IFN MEDIATED AUTOINFLAMMATORY DISEASES, NOMID AND CANDLE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 178-179
Author(s):  
S. Alehashemi ◽  
M. Garg ◽  
B. Sellers ◽  
A. De Jesus ◽  
A. Biancotto ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Whole Blood ◽  
Cell Activation ◽  
Immune Cell ◽  
Differentially Expressed ◽  
Neutrophilic Dermatosis ◽  
Healthy Controls ◽  
Differentially Expressed Proteins ◽  
Rna Seq ◽  
Before And After

Background:Systemic Autoinflammatory diseases present with sterile inflammation. NOMID (Neonatal-Onset Multisystem Inflammatory Disease) is caused by gain-of-function mutations inNLRP3and excess IL-1 production, presents with fever, neutrophilic dermatosis, aseptic meningitis, hearing loss and eye inflammation; CANDLE (Chronic Atypical Neutrophilic Dermatosis, Lipodystrophy and Elevated Temperature) is caused by loss-of-function mutations in proteasome genes that lead to type-1 interferon signaling, characterized by fever, panniculitis, lipodystrophy, cytopenia, systemic and pulmonary hypertension and basal ganglia calcification. IL-1 blockers are approved for NOMID and JAK-inhibitors show efficacy in CANDLE treatment.Objectives:We used proteomic analysis to compare differentially expressed proteins in active NOMID and CANDLE compared to healthy controls before and after treatment, and whole blood bulk RNA seq to identify the immune cell signatures.Methods:Serum samples from active NOMID (n=12) and CANDLE (n=7) before and after treatment (table 1) and age matched healthy controls (HC) (n=7) were profiled using the SomaLogic platform (n=1125 proteins). Differentially expressed proteins in NOMID and CANDLE were ranked after non-parametric tests for unpaired (NOMIDp<0.05, CANDLE,p<0.1) and paired (p<0.05) analysis and assessed by enriched Gene Ontology pathways and network visualization. Whole blood RNA seq was performed (NOMID=7, CANDLE=7, Controls =5) and RPKM values were used to assess immune cells signatures.Table 1.Patient’s characteristicsNOMIDN=12, Male =6CANDLEN=7, Male =6AgeMedian (range)12 (2, 28)16 (3, 20)Ethnicity%White (Hispanic)80 (20)100 (30)GeneticsNLRP3mutation(2 Somatic, 10 Germline)mutations in proteasome component genes(1 digenic, 6 Homozygous/compound Heterozygous)Before treatmentAfter treatmentBefore treatmentAfter treatmentCRPMedian (range) mg/L52 (16-110)5 (0-23)5 (0-101)1 (0-4)IFN scoremedian (range)0NA328 (211-1135)3 (0-548)Results:Compared to control, 205 proteins (127 upregulated, 78 downregulated) were significantly different at baseline in NOMID, compared to 163 proteins (101 upregulated, and 62 downregulated) in CANDLE. 134 dysregulated proteins (85 upregulated, 49 downregulated) overlapped in NOMID and CANDLE (Figure 1). Pathway analysis identified neutrophil and monocyte chemotaxis signature in both NOMID and CANDLE. NOMID patients had neutrophilia and active neutrophils. CANDLE patients exhibited active neutrophils in whole blood RNA. Endothelial cell activation was the most prominent non-hematopoietic signature and suggest distinct endothelial cell dysregulation in NOMID and CANDLE. In NOMID, the signature included neutrophil transmigration (SELE) endothelial cell motility in response to angiogenesis (HGF, VEGF), while in CANDLE the endothelial signatures included extracellular matrix protein deposition (COL8A) suggesting increased vascular stiffness. CANDLE patients had higher expression of Renin, 4 out of 7 had hypertension, NOMID patients did not have hypertension. Treatment with anakinra and baricitinib normalized 143 and 142 of dysregulated proteins in NOMID and CANDLE respectively.Conclusion:Differentially expressed proteins in NOMID and CANDLE are consistent with innate immune cell activation. Distinct endothelial cell signatures in NOMID and CANDLE may provide mechanistic insight into differences in vascular phenotypes. Treatment with anakinra and Baricitinib in NOMID and CANDLE leaves 30% and 13% of the dysregulated proteins unchanged.Acknowledgments:This work was supported by Intramural Research atNational Institute of Allergy Immunology and Infectious Diseases of National Institutes of Health, Bethesda, Maryland, the Center of Human Immunology and was approved by the IRB.Disclosure of Interests:None declared

scholarly journals MODL-16. ABEMACICLIB, A SELECTIVE CDK4/6 INHIBITOR, RESTRICTS GROWTH OF PEDIATRIC GLIAL-LINEAGE TUMORS IN VITRO AND IN VIVO

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii414-iii414
Author(s):  
Muh-Lii Liang ◽  
Tsung-Han Hsieh ◽  
Tai-Tong Wong
Keyword(s):  
Dna Repair ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Rna Seq ◽  
Downstream Target ◽  
Rb Phosphorylation ◽  
Glial Lineage

Abstract BACKGROUND Glial-lineage tumors constitute a heterogeneous group of neoplasms, comprising gliomas, oligodendrogliomas, and ependymomas, which account for 40%–50% of all pediatric central nervous system tumors. Advances in modern neuro-oncological therapeutics are aimed at improving neoadjuvant chemotherapy and deferring radiotherapy because radiation exposure may cause long-term side effects on the developing brain in young children. Despite aggressive treatment, more than half the high-grade gliomas (pHGGs) and one-third of ependymomas exhibit recurrence within 2 years of initial treatment. METHODS By using integrated bioinformatics and through experimental validation, we found that at least one gene among CCND1, CDK4, and CDK6 was overexpressed in pHGGs and ependymomas. RESULTS The use of abemaciclib, a highly selective CDK4/6 inhibitor, effectively inhibited cell proliferation and reduced the expression of cell cycle–related and DNA repair–related gene expression, which was determined through RNA-seq analysis. The efficiency of abemaciclib was validated in vitro in pHGGs and ependymoma cells and in vivo by using subcutaneously implanted ependymoma cells from patient-derived xenograft (PDX) in mouse models. Abemaciclib demonstrated the suppression of RB phosphorylation, downstream target genes of E2F, G2M checkpoint, and DNA repair, resulting in tumor suppression. CONCLUSION Abemaciclib showed encouraging results in preclinical pediatric glial-lineage tumors models and represented a potential therapeutic strategy for treating challenging tumors in children.

scholarly journals Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Regression Model ◽  
Target Genes ◽  
Cox Regression ◽  
Risk Group ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Prognostic Analysis ◽  
Significant Difference

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

scholarly journals Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xia Tang ◽  
Delong Feng ◽  
Min Li ◽  
Jinxue Zhou ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Rna Seq ◽  
Pairwise Interactions ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
First Time

Abstract Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p < 0.05), including p53, MAPK, and NAFLD signaling. Potential pairwise interactions between DE ncRNAs and mRNAs were fully characterized using in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

ASXL2 Is a Novel Mediator of RUNX1-ETO Transcriptional Function and Collaborates with RUNX1-ETO to Promote Leukemogenesis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 302-302
Author(s):  
Jean-Baptiste Micol ◽  
Nicolas Duployez ◽  
Alessandro Pastore ◽  
Robert Williams ◽  
Eunhee Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Hematopoietic Stem Cell ◽  
Binding Sites ◽  
Target Genes ◽  
Cell Function ◽  
Rna Seq ◽  
Hematopoietic Stem

Abstract Mutations in Addition of Sex Combs Like 1 (ASXL1) are common in patients with myeloid leukemias. More recently, mutations in ASXL2, a paralog of ASXL1 with ~40% shared amino acid homology, have been discovered to occur specifically in patients with acute myeloid leukemia (AML) patients bearing the RUNX1-ETO (AML1-ETO; RUNX1-RUNX1T1) translocation and are amongst the most common mutations in RUNX1-ETO AML (mutated in 20-25% of patients). Although ASXL1 is critical for Polycomb Repressive Complex 2 function in myeloid hematopoietic cells and loss of Asxl1 recapitulates key aspects of myelodysplastic syndrome (MDS), the function of ASXL2 in normal or malignant hematopoiesis is unknown. We therefore set out to perform a functional comparison of ASXL1and ASXL2on hematopoiesis and transcription and determine the functional basis for frequent mutations in RUNX1-ETO AML. In vitro analyses of ASXL2 insertion/deletion mutations revealed that these mutations resulted in substantial reduction of ASXL2 protein expression, stability, and half-life. We therefore generated Asxl2 conditional knockout (cKO) mice to delineate the effect of ASXL2 loss on hematopoiesis. Competitive (Fig. 1A) and noncompetitive transplantation revealed that Asxl2 or compound Asxl1/2 loss resulted in cell-autonomous, rapid defects of hematopoietic stem cell function, self-renewal, and number with peripheral blood leukopenia and thrombocytopenia but without any obvious MDS features- phenotypes distinct from Asxl1 cKO mice. Mice with heterozygous deletion of Asxl2 demonstrated an intermediate phenotype between control and homozygous cKO mice indicating a gene dosage effect of Asxl2 loss. RNA sequencing (RNA-seq) of hematopoietic stem/progenitor cells from Asxl2- and Asxl1-deficient mice revealed twenty-fold greater differentially expressed genes in Asxl2 cKO mice relative to Asxl1 cKO mice. Interestingly, genes differentially expressed with Asxl2 loss significantly overlapped with direct transcriptional targets of RUNX1-ETO, findings not seen in Asxl1 cKO mice (Fig. 1B). Asxl2 target genes appeared to also be targets of RUNX1, a key gene repressed by RUNX1-ETO to promote leukemogenesis. Consistent with this, genome-wide analysis of Asxl2 binding sites through anti-Asxl2 ChIP-seq revealed that Asxl2 binding sites substantially overlap with those of Runx1. Overall, the above data suggest that Asxl2 may be a critical mediator of RUNX1-ETO mediated leukemogenesis by affecting the expression of RUNX1 and/or RUNX1-ETO target genes. RNA-seq of primary RUNX1-ETO AML patient samples revealed that ASXL2-mutant RUNX1-ETO patients form a distinct transcriptional subset of RUNX1-ETO AML (Fig. 1C) suggesting a specific role of ASXL2 in leukemogenesis. To functionally interrogate the role of ASXL2 loss in RUNX1-ETO mediated leukemogenesis we first utilized an in vitro model with RNAi-mediated depletion of ASXL1 or ASXL2 in the SKNO1 cell line (the only ASXL-wildtype human RUNX1-ETO cell line). RNA-seq revealed distinct target genes dysregulated by ASXL1 versus ASXL2 loss in these cells without any significant overlap. Anti-ASXL2, RUNX1, and RUNX1-ETO ChIPSeq in SKNO1 cells revealed significant co-occupancy of ASXL2 with RUNX1 and RUNX1-ETO binding sites. Moreover, analysis of histone modification ChIPSeq revealed an enrichment in intergenic and enhancer H3K4me1 abundance following ASXL2 loss in SKNO1 cells. Next, to understand the in vivo effects of Asxl2 loss in the context of RUNX1-ETO, we performed retroviral bone marrow (BM) transplantation assays using RUNX1-ETO9a in Asxl2 cKO mice. In contrast to the failure of hematopoietic stem cell function with Asxl2 deletion alone, mice reconstituted with BM cells expressing RUNX1-ETO9a in Asxl2-deficient background had a shortened leukemia-free survival compared to Asxl2 -wildtype control. Overall, these data reveal that ASXL2 is required for hematopoiesis and has differing biological and transcriptional functions from ASXL1. Moreover, this work identifies ASXL2 as a novel mediator of RUNX1-ETOtranscriptional function and provides a new model of penetrant RUNX1-ETO AML based on genetic events found in a substantial proportion of t(8;21) AML patients. Further interrogation of the enhancer alterations generated by ASXL2 loss in RUNX1-ETO AML may highlight new therapeutic approaches for this subset of AML. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical role and biological function of CDK5 in hepatocellular carcinoma: A study based on immunohistochemistry, RNA-seq and in vitro investigation

Oncotarget ◽  
2017 ◽  
Vol 8 (65) ◽  
pp. 108333-108354 ◽  
Author(s):  
Rui Zhang ◽  
Peng Lin ◽  
Hong Yang ◽  
Yun He ◽  
Yi-Wu Dang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Biological Function ◽  
Rna Seq ◽  
Clinical Role ◽  
In Vitro Investigation

scholarly journals ARID1A Is a Prognostic Biomarker and Associated with Immune Infiltrates in Hepatocellular Carcinoma

2022 ◽  
Vol 2022 ◽  
pp. 1-14
Author(s):  
Yuanyuan Feng ◽  
Xinfang Tang ◽  
Changcheng Li ◽  
Ying Su ◽  
Xiaoyu Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Migration And Invasion ◽  
Risk Indicator ◽  
Immune Cell Infiltration

Objective. ARID1A has been discovered as a potential cancer biomarker. But its role in hepatocellular carcinoma (HCC) is subject to considerable dispute. Methods. The relationship between ARID1A and clinical factors was investigated. Clinicopathological variables related to overall survival in HCC subjects were identified using Cox and Kaplan–Meier studies. The connection between immune infiltrating cells and ARID1A expression was investigated using the tumor Genome Atlas (TCGA) dataset for gene set enrichment analysis (GSEA). Finally, a cell experiment was used to confirm it. Results. The gender and cancer topography (T) categorization of HCC were linked to increased ARID1A expression. Participants with advanced levels of ARID1A expression had a worse prognosis than someone with lower levels. ARID1A was shown to be a risk indicator of overall survival on its own. ARID1A expression is inversely proportional to immune cell infiltration. In vitro, decreasing ARID1A expression substantially slowed the cell cycle and decreased HCC cell proliferation, migration, and invasion. Conclusion. The expression of ARID1A could be used to predict the outcome of HCC. It is closely related to tumor immune cell infiltration.

scholarly journals Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

2018 ◽  
Vol 237 (2) ◽  
pp. 123-137 ◽  
Author(s):  
Min Hu ◽  
Yuehui Zhang ◽  
Jiaxing Feng ◽  
Xue Xu ◽  
Jiao Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Metformin Therapy ◽  
Before And After ◽  
Elevated Expression ◽  
Targeted Gene Expression ◽  
First Time

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

scholarly journals EZH1/2 inhibition augments the anti-tumor effects of sorafenib in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuko Kusakabe ◽  
Tetsuhiro Chiba ◽  
Motohiko Oshima ◽  
Shuhei Koide ◽  
Ola Rizq ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Target Genes ◽  
Antitumor Effects ◽  
Sorafenib Treatment ◽  
Ezh2 Expression ◽  
Combined Use

AbstractBoth EZH2 and its homolog EZH1 function as histone H3 Lysine 27 (H3K27) methyltransferases and repress the transcription of target genes. Dysregulation of H3K27 trimethylation (H3K27me3) plays an important role in the development and progression of cancers such as hepatocellular carcinoma (HCC). This study investigated the relationship between the expression of EZH1/2 and the level of H3K27me3 in HCC. Additionally, the role of EZH1/2 in cell growth, tumorigenicity, and resistance to sorafenib were also analyzed. Both the lentiviral knockdown and the pharmacological inhibition of EZH1/2 (UNC1999) diminished the level of H3K27me3 and suppressed cell growth in liver cancer cells, compared with EZH1 or EZH2 single knockdown. Although a significant association was observed between EZH2 expression and H3K27me3 levels in HCC samples, overexpression of EZH1 appeared to contribute to enhanced H3K27me3 levels in some EZH2lowH3K27me3high cases. Akt suppression following sorafenib treatment resulted in an increase of the H3K27me3 levels through a decrease in EZH2 phosphorylation at serine 21. The combined use of sorafenib and UNC1999 exhibited synergistic antitumor effects in vitro and in vivo. Combination treatment canceled the sorafenib-induced enhancement in H3K27me3 levels, indicating that activation of EZH2 function is one of the mechanisms of sorafenib-resistance in HCC. In conclusion, sorafenib plus EZH1/2 inhibitors may comprise a novel therapeutic approach in HCC.

scholarly journals Vitamin D: Possible Therapeutic Roles in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Isaacson B. Adelani ◽  
Oluwakemi A. Rotimi ◽  
Emmanuel N. Maduagwu ◽  
Solomon O. Rotimi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vitamin D ◽  
Target Genes ◽  
Metabolizing Enzymes ◽  
Unique Type ◽  
Functional Roles ◽  
Anticancer Effects ◽  
Biological Responses

Hepatocellular carcinoma (HCC) is a unique type of liver cancer instigated by underlying liver diseases. Pre-clinical evidence suggests that HCC progression, like other cancers, could be aided by vitamin D deficiency. Vitamin D is a lipid-soluble hormone usually obtained through sunlight. Vitamin D elucidates its biological responses by binding the vitamin D receptor; thus, promoting skeletal mineralization, and maintain calcium homeostasis. Other reported Vitamin D functions include specific roles in proliferation, angiogenesis, apoptosis, inflammation, and cell differentiation. This review highlighted studies on vitamin D’s functional roles in HCC and discussed the specific therapeutic targets from various in vivo, in vitro and clinical studies over the years. Furthermore, it described recent advancements in vitamin D’s anticancer effects and its metabolizing enzymes’ roles in HCC development. In summary, the review elucidated specific vitamin D-associated target genes that play critical functions in the inhibition of tumorigenesis through inflammation, oxidative stress, invasion, and apoptosis in HCC progression.

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