Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An OX40L mRNA vaccine inhibits the growth of hepatocellular carcinoma.

ABSTRACT: mRNA cancer vaccines show therapeutic potential for malignant tumors, including hepatocellular carcinoma (HCC). We optimized and synthesized stable mRNA encoding costimulator Oxford 40 ligand (OX40L). For systemic delivery, OX40L mRNAs were loaded into lipid nanoparticles (LNPs). The expression and costimulatory effects of OX40L were investigated in vitro. OX40L was expressed on the cell surface and costimulated T cells. In vivo, intratumoral injection of LNPs encapsulating OX40L mRNAs significantly reduced tumor growth and increased the survival of mice bearing H22 tumors. Importantly, CD4+ and CD8+ T cells were significantly increased in the OX40L mRNA group in vivo. Taken together, our findings provide a promising clinical strategy for immunotherapy for HCC using mRNA vaccines.

SUBMITTER: Deng Z

PROVIDER: S-EPMC9606466 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An OX40L mRNA vaccine inhibits the growth of hepatocellular carcinoma.

Deng Zhuoya Z Yang Hao H Tian Yuying Y Liu Zherui Z Sun Fang F Yang Penghui P

Frontiers in oncology 20221013

mRNA cancer vaccines show therapeutic potential for malignant tumors, including hepatocellular carcinoma (HCC). We optimized and synthesized stable mRNA encoding costimulator Oxford 40 ligand (OX40L). For systemic delivery, OX40L mRNAs were loaded into lipid nanoparticles (LNPs). The expression and costimulatory effects of OX40L were investigated in vitro. OX40L was expressed on the cell surface and costimulated T cells. In vivo, intratumoral injection of LNPs encapsulating OX40L m ...[more]

PMID: 36313716

Similar Datasets

MiR-940 inhibits hepatocellular carcinoma growth and correlates with prognosis of hepatocellular carcinoma patients.

Project description:Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death in China. Deregulation of microRNA (miRNA) contributes to HCC development by influencing cell growth, apoptosis, migration or invasion. It has been proved that miR-940 plays important roles in various cancers. Here we investigated the role of miR-940 in HCC. We found that miR-940 was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-940 expression in HCC tissues significantly correlated with the reduced patient's survival rate. Overexpression of miR-940 inhibited HCC cell line growth and induced cell apoptosis, and vice versa. Estrogen-related receptor gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis. In conclusion, we found that a lower level of miR-940 in HCC promoted cellular proliferation via ESRRG, which may lead to the short survival period of HCC patients.

| S-EPMC4520632 | biostudies-literature

ShRNA-targeted centromere protein A inhibits hepatocellular carcinoma growth.

Project description:BACKGROUND: Centromere protein A (CENP-A) plays important roles in cell-cycle regulation and genetic stability. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: CENP-A expression at the mRNA and protein levels was examined in 20 pairs of fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for CENP-A was performed on 80 paraffin-embedded HCC specimens, and the clinical significance of its expression was analyzed. A human HCC cell line HepG2 with high abundance of CENP-A was used to study the effects of manipulating CENP-A on HCC growth. Quantitative real-time polymerase chain reaction arrays and Western blot analysis were employed to identify the cell-cycle control- and apoptosis-related genes regulated by CENP-A. The results showed that CENP-A was aberrantly overexpressed in HCCs relative to adjacent nontumor tissues. This overexpression was significantly associated with positive serum HBsAg status, increased histological grade, high Ki-67 index and P53 immunopositivity. Knockdown of CENP-A in HepG2 cells reduced cell proliferation, blocked cell cycle at the G1 phase, and increased apoptosis. The antiproliferative effects of CENP-A silencing were also observed in vivo. Conversely, CENP-A overexpression promoted HCC cell growth and reduced apoptosis. Furthermore, many genes implicated in cell-cycle regulation and apoptosis, including CHK2, P21waf1, P27 Kip1, SKP2, cyclin G1, MDM2, Bcl-2, and Bax, were deregulated by manipulating CENP-A. CONCLUSIONS/SIGNIFICANCE: Overexpression of CENP-A is frequently observed in HCC. Targeting CENP-A can inhibit HCC growth, likely through the regulation of a large number genes involved in cell-cycle progression and apoptosis, and thereby represents a potential therapeutic strategy for this malignancy.

| S-EPMC3058037 | biostudies-literature

MicroRNA-99a inhibits hepatocellular carcinoma growth and correlates with prognosis of patients with hepatocellular carcinoma.

Project description:In our in-depth analysis carried out by the Illumina Solexa massive parallel signature sequencing, microRNA-99a (miR-99a) was found to be the sixth abundant microRNA in the miRNome of normal human liver but was markedly down-regulated in hepatocellular carcinoma (HCC). Compelling evidence has suggested the important roles of microRNAs in HCC development. However, the biological function of miR-99a deregulation in HCC remains unknown. In this study, we found that miR-99a was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-99a expression in HCC tissues significantly correlated with shorter survival of HCC patients, and miR-99a was identified to be an independent predictor for the prognosis of HCC patients. Furthermore, restoration of miR-99a dramatically suppressed HCC cell growth in vitro by inducing the G(1) phase cell cycle arrest. Intratumoral injection of cholesterol-conjugated miR-99a mimics significantly inhibited tumor growth and reduced the ?-fetoprotein level in HCC-bearing nude mice. Insulin-like growth factor 1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) were further characterized as the direct targets of miR-99a. Furthermore, protein levels of IGF-1R and mTOR were found to be inversely correlated with miR-99a expression in HCC tissues. miR-99a mimics inhibited IGF-1R and mTOR pathways and subsequently suppressed expression of cell cycle-related proteins, including cyclin D1 in HCC cells. Conclusively, miR-99a expression was frequently down-regulated in HCC tissues and correlates with the prognosis of HCC patients, thus proposing miR-99a as a prospective prognosis predictor of HCC. miR-99a suppresses HCC growth by inducing cell cycle arrest, suggesting miR-99a as potential tumor suppressor for HCC therapeutics.

| S-EPMC3196113 | biostudies-literature

UPF1 Inhibits Hepatocellular Carcinoma Growth through DUSP1/p53 Signal Pathway.

Project description:Human hepatocellular carcinoma (HCC) has a high mortality rate because of the dearth of effective treatments. Multiple studies have shown that overexpression of UPF1, a key nonsense-mediated mRNA decay (NMD) factor, reduces HCC growth through various cell signaling pathways. However, the mechanism by which UPF1 expression retards HCC proliferation through the regulation of RNA stability remains unclear. By employing various UPF1 variants and transcriptome analysis, we revealed that overexpression of UPF1 variants, not UPF1-mediated NMD, reduces HCC tumorigenesis. Additionally, UPF1 variant overexpression reduced tumorigenesis in xenografted mice. Transcriptome analysis indicated that the level of dual specificity phosphatase 1 (DUSP1) was increased by UPF1 variants via posttranscriptional regulation. The UPF1 overexpression-mediated increase of DUSP1 activated tumor suppressor signaling, ultimately inhibiting cell growth. In this study, we highlighted the function of UPF1 as a tumor suppressor in HCC growth.

| S-EPMC9029930 | biostudies-literature

LHPP inhibits hepatocellular carcinoma cell growth and metastasis.

Project description:Hepatocellular carcinoma (HCC) has a poor prognosis, owing to its high potential for growth and metastasis. In this study, we aimed to investigate the roles of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP)in human HCCcell growth and metastasis. We analyzed the LHPP expression level in human HCC tissues paired normal tissues in the Oncomine database, and assessed the relationship between the LHPP expression levels with HCC patient's overall survival and the prognostic value of LHPP in human HCC by Kaplan-Meier survival analysis. Real-time PCR and Western Blot were used to examine the expression levels of LHPP in normal liver cell line (LO2) and human HCC cell lines (SMCC-7721, HepG2, Huh7, MHCC-97 H, and LM3). Through lentivirus infection, we established human HCC stable cell lines (Huh7 and LM3) overexpressing LHPP. Then, we detected these cell viability, colony , and invasion. Subsequently, we performed the gene set enrichment analysis (GSEA) for the RNA-seq data of HCC patients from TCGA. Finally, we examined the expression level of several oncogenes, including CCNB1, PKM2, MMP7, and MMP9, in these cells via real-time PCR assay. Here, we found thatLHPPis significantly downregulated in the human HCC tissues paired normal tissues. Furthermore, the high expression level of LHPP is associated with better clinical outcomes in human HCC. Overexpression of LHPPinhibitscell growth and metastasis in human HCC cells, and LHPP expression levels negatively correlate with cell cycle and metastasis in HCC tissues. Moreover, the level of LHPP is negatively correlated with CCNB1, PKM2, MMP7, and MMP9 in human HCC cells and HCC tissues. These findings highlight a novel tumor suppressor in human HCC growth and metastasis, and provide a promising diagnostic and prognostic factor for humanHCC.

| S-EPMC7469522 | biostudies-literature

ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth.

Project description:The M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in regulation of the Warburg effect, which is characterized by the preference for aerobic glycolysis over oxidative phosphorylation for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene and is a potential therapeutic target. Antisense oligonucleotides (ASO) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform have been shown to induce apoptosis in cultured glioblastoma cells when delivered by lipofection. Here, we explore the potential of ASO-based PKM splice switching as a targeted therapy for liver cancer. A more potent lead constrained-ethyl (cEt)/DNA ASO induced PKM splice switching and inhibited the growth of cultured hepatocellular carcinoma (HCC) cells. This PKM isoform switch increased pyruvate-kinase activity and altered glucose metabolism. In an orthotopic HCC xenograft mouse model, the lead ASO and a second ASO targeting a nonoverlapping site inhibited tumor growth. Finally, in a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis, without observable toxicity. These results lay the groundwork for a potential ASO-based splicing therapy for HCC.SignificanceAntisense oligonucleotides are used to induce a change in PKM isoform usage in hepatocellular carcinoma, reversing the Warburg effect and inhibiting tumorigenesis.

| S-EPMC8898261 | biostudies-literature

Targeting RORγ inhibits the growth and metastasis of hepatocellular carcinoma.

Project description:Approximately 80%-90% of hepatocellular carcinomas (HCC) occur in a premalignant environment of fibrosis and abnormal extracellular matrix (ECM), highlighting an essential role of ECM in the tumorigenesis and progress of HCC. However, the determinants of ECM in HCC are poorly defined. Here, we show that nuclear receptor RORγ is highly expressed and amplified in HCC tumors. RORγ functions as an essential activator of the matrisome program via directly driving the expression of major ECM genes in HCC cells. Elevated RORγ increases fibronectin-1 deposition, cell-matrix adhesion, and collagen production, creating a favorable microenvironment to boost liver cancer metastasis. Moreover, RORγ antagonists effectively inhibit tumor growth and metastasis in multiple HCC xenografts and immune-intact models, and they effectively sensitize HCC tumors to sorafenib therapy in mice. Notably, elevated RORγ expression is associated with ECM remodeling and metastasis in patients with HCC. Taken together, we identify RORγ as a key player of ECM remodeling in HCC and as an attractive therapeutic target for advanced HCC.

| S-EPMC10928303 | biostudies-literature

Cryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin-6/STAT3 signalling.

Project description:BackgroundDiverse signalling pathways are involved in carcinogenesis and one of such pathways implicated in many cancers is the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signalling pathway. Therefore, inhibition of this pathway is targeted as an anti-cancer intervention. This study aimed to establish the effect of cryptolepine, which is the main bioactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, on the IL-6/STAT3 signalling pathway.MethodsFirst, the effect of cryptolepine on the IL-6/STAT3 pathway in human hepatoma cells (HepG2 cells) was screened using the Cignal Finder Multi-Pathway Reporter Array. Next, to confirm the effect of cryptolepine on the IL-6/STAT3 signalling pathway, the pathway was activated using 200 ng/mL IL-6 in the presence of 0.5-2 μM cryptolepine. The levels of total STAT3, p-STAT3 and IL-23 were assessed by ELISA.ResultsCryptolepine downregulated 12 signalling pathways including the IL-6/STAT3 signalling pathway and upregulated 17 signalling pathways. Cryptolepine, in the presence of IL-6, decreased the levels of p-STAT3 and IL-23 in a dose-dependent fashion.ConclusionOur results demonstrated that cryptolepine inhibits the IL-6/STAT3 signalling pathway, and therefore cryptolepine-based remedies such as Cryptolepis sanguinolenta could potentially be used as an effective immunotherapeutic agent for hepatocellular carcinoma and other cancers.

| S-EPMC8170807 | biostudies-literature

miR-206 inhibits the growth of hepatocellular carcinoma cells via targeting CDK9.

Project description:miR-206 plays an important role in regulating the growth of multiple cancer cells. Cyclin-dependent kinase 9 (CDK9) stimulates the production of abundant prosurvival proteins, leading to impaired apoptosis of cancer cells. However, it is unknown whether CDK9 is involved in the miR-206-mediated growth suppression of hepatocellular carcinoma (HCC) cells. In this study, we found that the expression level of miR-206 was significantly lower in HCC cell lines than that in normal hepatic cell line (L02). Meanwhile, CDK9 was upregulated in HCC cell lines. Moreover, miR-206 downregulated CDK9 in HCC cells via directly binding to its mRNA 3' UTR, which resulted in a decrease of RNA PolII Ser2 phosphorylation and Mcl-1 level. Additionally, miR-206 suppressed the cell proliferation, and induced cell cycle arrest and apoptosis. Similarly, silence or inhibition of CDK9 also repressed the cell proliferation, and induced cell cycle arrest and apoptosis. Taken together, the results demonstrated that miR-206 inhibited the growth of HCC cells through targeting CDK9, suggesting that the miR-206-CDK9 pathway may be a novel target for the treatment of HCC.

| S-EPMC5633544 | biostudies-literature

PFKFB3 blockade inhibits hepatocellular carcinoma growth by impairing DNA repair through AKT.

Project description:Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key molecule of glucose metabolism in cytoplasm, has been found in various tumors. Emerging evidence has suggested that PFKFB3 is also located in the nucleus and apparent in regulatory functions other than glycolysis. In this study, we found that PFKFB3 expression is associated with hepatocellular carcinoma (HCC) growth and located mainly in the nucleus of tumor cells. PFKFB3 overexpression was associated with large tumor size (p = 0.04) and poor survival of patients with HCC (p = 0.027). Knockdown of PFKFB3 inhibited HCC growth, not only by reducing glucose consumption but also by damaging the DNA repair function, leading to G2/M phase arrest and apoptosis. In animal studies, overexpression of PFKFB3 is associated with increased tumor growth. Mechanistically, PFKFB3 silencing decreased AKT phosphorylation and reduced the expression of ERCC1, which is an important DNA repair protein. Moreover, PFK15, a selective PFKFB3 inhibitor, significantly inhibited tumor growth in a xenograft model of human HCC. PFKFB3 is a potential novel target in the treatment of HCC.

| S-EPMC5861039 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data