Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel roles of TMEM100: inhibition metastasis and proliferation of hepatocellular carcinoma.

ABSTRACT: Transmembrane protein 100 (TMEM100) was activated by ALK1/TGF-? signaling. We found that TMEM100 was decreased in hepatocellular carcinoma (HCC) tissues and in highly metastatic cell lines. Overexpressed of TMEM100 inhibited invasion, migration and proliferation. Low levels of TMEM100 were associated with cirrhosis, tumor size, Tumor nodule number, TNM stage, BCLC stage, Edmondson-Steiner Stage and vein invasion. Furthermore, TMEM100 was an independent risk factor for overall survival (P = 0.03) and disease-free survival (P = 0.019). The current findings suggest that TMEM100 functions as a tumor suppressor in HCC metastasis and proliferation.

SUBMITTER: Ou D

PROVIDER: S-EPMC4627315 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Novel roles of TMEM100: inhibition metastasis and proliferation of hepatocellular carcinoma.

Ou Dipeng D Yang Hao H Hua Dong D Xiao Shuai S Yang Lianyue L

Oncotarget 20150701 19

Transmembrane protein 100 (TMEM100) was activated by ALK1/TGF-β signaling. We found that TMEM100 was decreased in hepatocellular carcinoma (HCC) tissues and in highly metastatic cell lines. Overexpressed of TMEM100 inhibited invasion, migration and proliferation. Low levels of TMEM100 were associated with cirrhosis, tumor size, Tumor nodule number, TNM stage, BCLC stage, Edmondson-Steiner Stage and vein invasion. Furthermore, TMEM100 was an independent risk factor for overall survival (P = 0.03) ...[more]

PMID: 25978032

Similar Datasets

Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome.

Project description:The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β secretion. Inflammasome activation is mediated by NLR proteins that respond to stimuli. Among NLRs, NLRP3 senses the widest array of stimuli. NLRP3 inflammasome plays an important role in the development of many cancer types. However, Whether NLRP3 inflammasome plays an important role in the process of hepatocellular carcinoma (HCC) is still unknown. Here, the anticancer effect of luteoloside, a naturally occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, against HCC cells and the underlying mechanisms were investigated. Luteoloside significantly inhibited the proliferation of HCC cells in vitro and in vivo. Live-cell imaging and transwell assays showed that the migration and invasive capacities of HCC cells, which were treated with luteoloside, were significantly inhibited compared with the control cells. The inhibitory effect of luteoloside on metastasis was also observed in vivo in male BALB/c-nu/nu mouse lung metastasis model. Further studies showed that luteoloside could significantly reduce the intracellular reactive oxygen species (ROS) accumulation. The decreased levels of ROS induced by luteoloside was accompanied by decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by luteoloside resulted in inhibition of IL-1β. Thus, luteoloside exerts its inhibitory effect on proliferation, invasion and metastasis of HCC cells through inhibition of NLRP3 inflammasome. Our results indicate that luteoloside can be a potential therapeutic agent not only as an adjuvant therapy for HCC, but also, in the control and prevention of metastatic HCC.

| S-EPMC3935965 | biostudies-literature

A novel biomarker Linc00974 interacting with KRT19 promotes proliferation and metastasis in hepatocellular carcinoma.

Project description:Location-associated long noncoding RNA (lncRNA) was reported to interact with target protein via a cis-regulatory process especially for the Flank10kb class lncRNA. Based on this theory, we aimed to explore the regulatory mechanisms of Linc00974 and KRT19 (an lncRNA beyond the Flank10kb class with protein) when we first confirmed the aberrant expression in hepatocellular carcinoma in a previous study. Knockdown of Linc00974 resulted in an inhibition of cell proliferation and invasion with an activation of apoptosis and cell cycle arrest in vitro, which was also validated by a subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo. We further investigated the interaction pattern of Linc00974 and KRT19. MiR-642 was identified, by acting as the competing endogenous RNA in regulating Linc00974 and KRT19. Linc00974 was increased owing to an abnormal hypomethylation promoter, which induced the upregulation of KRT19 via ceRNA interaction, resulting in the activation of the Notch and TGF-? pathways as detected by cDNA microarray. We also discovered Linc00974F-1 stably expressed in the plasma. By the combined analysis of Linc00974F-1 with CYFRA21-1, we found that these joint indicators predicted growth and metastasis of tumor in HCC patients. In conclusion, the combination of Linc00974 and KRT19 may be novel indices for clinical diagnosis of tumor growth and metastasis in HCC, while Linc00974 may become a potential therapeutic target for the prevention of HCC progression.

| S-EPMC4649834 | biostudies-other

LBH589 Inhibits proliferation and metastasis of hepatocellular carcinoma via inhibition of gankyrin/STAT3/Akt pathway.

Project description:BackgroundGankyrin has shown to be overexpressed in human liver cancers and plays a complex role in hepatocarcinogenesis. Panobinostat (LBH589), a new hydroxamic acid-derived histone deacetylase inhibitor has shown promising anticancer effects recently. Here, we investigated the potential of LBH589 as a form of treatment for hepatocellular carcinoma (HCC).MethodsGankyrin plasmid was transfected into HCC cells, and the cells were selected for more than 4 weeks by incubation with G418 for overexpression clones. The therapeutic effects of LBH589 were evaluated in vitro and in vivo. Cell proliferation, apoptosis, cell cycle, invasive potential, and epithelial-mesenchy-mal transition (EMT) were examined.ResultsLBH589 significantly inhibited HCC growth and metastasis in vitro and in vivo. Western blotting analysis indicated that LBH589 could decrease the expression of gankyrin and subsequently reduced serine-phosphorylated Akt and tyrosine-phosphorylated STAT3 expression although the total Akt and STAT3 were unaffected. LBH589 inhibited metastasis in vitro via down-regulation of N-cadherin, vimentin, TWIST1, VEGF and up-regulation of E-cadherin. LBH589 also induced apoptosis and G1 phase arrest in HCC cell lines. Ectopic expression of gankyrin attenuated the effects of LBH589, which indicates that gankyrin might play an important role in LBH589 mediated anticancer effects. Lastly, in vivo study indicated that LBH589 inhibited tumor growth and metastasis, without discernable adverse effects comparing to control group, with abrogating gankyrin/STAT3/Akt pathway.ConclusionsOur results suggested that LBH589 could inhibit HCC growth and metastasis through down-regulating gankyrin/STAT3/Akt pathway. LBH589 may present itself as a novel therapeutic strategy for HCC.

| S-EPMC3853770 | biostudies-literature

SPC25 may promote proliferation and metastasis of hepatocellular carcinoma via p53.

Project description:Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis and high mortality. To identify key genes associated with HCC and the underlying mechanisms, we performed weighted correlation network analysis (WGCNA) of potential key genes of HCC. We identified 17 key genes closely related to HCC by yellow module combined with PPI analysis. Verification of the role of these genes revealed that SPC25 knockdown results in a significant decrease in proliferation and metastasis of HCC cells and increased protein levels of components of the p53 pathway in vitro. In summary, we identified that SPC25 is a potential tumor-promoting factor in HCC and may act via the p53 pathway.

| S-EPMC7327911 | biostudies-literature

LDLR inhibition promotes hepatocellular carcinoma proliferation and metastasis by elevating intracellular cholesterol synthesis through the MEK/ERK signaling pathway.

Project description:ObjectiveAdaptive rewiring of cancer energy metabolism has received increasing attention. By binding with LDLs, LDLRs make most of the circulating cholesterol available for cells to utilize. However, it remains unclear how LDLR works in HCC development by affecting cholesterol metabolism.MethodsDatabase analyses and immunohistochemical staining were used to identify the clinical significance of LDLR in HCC. A transcriptome analysis was used to reveal the mechanism of LDLR aberration in HCC progression. A liver orthotopic transplantation model was used to evaluate the role of LDLR in HCC progression in vivo.ResultsDownregulation of LDLR was identified as a negative prognostic factor in human HCC. Reduced expression of LDLR in HCC cell lines impaired LDL uptake but promoted proliferation and metastasis in vitro and in vivo. Mechanistically, increasing intracellular de novo cholesterol biosynthesis was the chief contributor to malignant behaviors caused by LDLR inhibition, which could be rescued by simvastatin. Activation of the MEK/ERK pathway by LDLR downregulation partially contributed to intracellular cholesterol synthesis in HCC.ConclusionsDownregulation of LDLR may elevate intracellular cholesterol synthesis to accelerate proliferation and motility through a mechanism partially attributed to stimulation of the MEK/ERK signaling pathway. Repression of intracellular cholesterol synthesis with statins may constitute a targetable liability in the context of lower LDLR expression in HCC.

| S-EPMC8102998 | biostudies-literature

Cyclin Y Modulates the Proliferation, Invasion, and Metastasis of Hepatocellular Carcinoma Cells.

Project description:BACKGROUND Cyclin Y (CCNY) is a member of the cyclin family of proteins that regulate the cell cycle. The aims of this study were to compare the expression of CCNY in normal liver and human hepatocellular carcinoma (HCC), in normal and HCC cell lines, and in mouse HCC tumor xenografts. MATERIAL AND METHODS Tumor tissues from 55 patients diagnosed with HCC were studied for CCNY expression. Human HCC cell lines, SK-Hep1, HepG2, HEP3B, HuH7 and L02 were studied using the MTT cell proliferation assay, cell apoptosis, transwell and wound healing assays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to measure CCNY expression. Indirect immunofluorescence was used to assess cell apoptosis. In vivo xenograft mouse model was constructed and examined histologically. RESULTS Expression of CCNY in human HCC tumor tissues was significantly increased when compared with adjacent normal liver (all P<0.05). HCC cells grown in vitro showed significantly increased expression of CCNY, cell proliferation, and migration, and a reduced rate of apoptosis, compared with cells with CCNY knockdown (siRNA) (all P<0.05). In the xenograft mouse model, tumor volume and weight in the CCNY overexpression group were significantly increased, compared with CCNY knockdown (siRNA) group (all P<0.05). CONCLUSIONS In tissue samples of human HCC, and human HCC cell lines, increased expression of CCNY was significantly associated with cell proliferation and migration. Further studies are recommended to evaluate the role of CCNY as a potential diagnostic biomarker or target for treatment in human HCC.

| S-EPMC5873331 | biostudies-literature

MiR-371 promotes proliferation and metastasis in hepatocellular carcinoma by targeting PTEN.

Project description:Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. MiR-371 has recently emerged as an important regulator in tumorigenesis, and may serve as a biomarker for malignant tumors. We transfected miR-371 or its inhibitor in two human HCC cell lines, then used 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, soft agar colony formation, and transwell migration assays to evaluate the effects on cell proliferation, migration, and invasion. We found that miR-371 was positively correlated with HCC metastasis and poor prognosis in the inflicted patients, and the high expression of miR-371 was promoted, whereas a low level of miR-371 depressed cell proliferation and invasion. We found PTEN to be a direct target of miR-371. The overexpression or knockdown of PTEN exhibited the opposite effects from those of miR-371 on cell proliferation and migration. Our study demonstrates that miR-371 promotes proliferation and metastasis in HCC by targeting PTEN. [BMB Reports 2019; 52(5): 312-317].

| S-EPMC6549920 | biostudies-literature

Inhibition of Cell Proliferation and Metastasis by Scutellarein Regulating PI3K/Akt/NF-κB Signaling through PTEN Activation in Hepatocellular Carcinoma.

Project description:Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against several cancers. Human hepatocellular carcinoma (HCC) is major cancer type due to its poor prognosis even after treatment with chemotherapeutic drugs, which causes a variety of side effects in patients. Therefore, efforts have been made to develop effective biomarkers in the treatment of HCC in order to improve therapeutic outcomes using natural based agents. The current study used SCU as a treatment approach against HCC using the HepG2 cell line. Based on the cell viability assessment up to a 200 μM concentration of SCU, three low-toxic concentrations of (25, 50, and 100) μM were adopted for further investigation. SCU induced cell cycle arrest at the G2/M phase and inhibited cell migration and proliferation in HepG2 cells in a dose-dependent manner. Furthermore, increased PTEN expression by SCU led to the subsequent downregulation of PI3K/Akt/NF-κB signaling pathway related proteins. In addition, SCU regulated the metastasis with EMT and migration-related proteins in HepG2 cells. In summary, SCU inhibits cell proliferation and metastasis in HepG2 cells through PI3K/Akt/NF-κB signaling by upregulation of PTEN, suggesting that SCU might be used as a potential agent for HCC therapy.

| S-EPMC8396260 | biostudies-literature

The novel miR-1269b-regulated protein SVEP1 induces hepatocellular carcinoma proliferation and metastasis likely through the PI3K/Akt pathway.

Project description:Decreased intercellular adhesion is a key step in the metastasis and recurrence of many cancers, including hepatocellular carcinoma (HCC). SVEP1 is an important cell adhesion molecule that plays a key role in regulating intercellular adhesion and embryonic lymphatic development. However, the expression patterns and roles of SVEP1 in HCC are still largely unknown. We identified SVEP1 expression by analyzing 220 HCC samples from our cancer center. TCGA and GEO online-databases were used for data calibration and validation. SVEP1 was differentially expressed in two groups of HCCs with different risks of recurrence and was deemed as an independent risk factor for the prognosis of HCC. The expression of SVEP1 is negatively related to the proliferation and metastasis of HCC. Downregulation of SVEP1 expression promoted in vitro HCC cell migration, chemotaxis, invasion and proliferation, as well as in vivo tumor growth, local invasion and metastasis in a mouse model. Bioinformatic analysis and RT-PCR results showed that miR-1269b expression is negatively correlated with the SVEP1 expression and the prognosis of HCC patients. Further experiments showed that miR-1269b directly targets and downregulates the expression of SVEP1, which further induces the phosphorylation of Akt at thr308. These regulatory effects ultimately mediate the proliferation and metastasis of HCC cells. SVEP1 could serve as a promising prognostic marker of HCC. MiR-1269b downregulates SVEP1 expression and promotes HCC proliferation and metastasis likely through the PI3k/Akt signaling pathway.

| S-EPMC7200779 | biostudies-literature

HMGCS2 Mediates Ketone Production and Regulates the Proliferation and Metastasis of Hepatocellular Carcinoma.

Project description:Hepatocellular carcinoma (HCC) is the most common primary malignant tumor worldwide; however, the traditional therapeutic approaches and survival rates are still limited. To improve current therapies, it is necessary to investigate the molecular mechanisms underlying liver cancer and to identify potential therapeutic targets. The aims of this study were to verify the mechanisms and therapeutic potential of the ketogenesis rate-limiting enzyme 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in HCC. Immunohistochemical staining of human liver disease tissue arrays showed that HMGCS2 is abundantly expressed in normal liver tissues but is downregulated in cirrhosis and HCC tissues. In HCC patients, lower HMGCS2 expression was correlated with higher pathological grades and clinical stages. In our investigation of the molecular mechanisms of HMGCS2 in HCC, we showed that knockdown of HMGCS2 decreased ketone production, which promoted cell proliferation, cell migration, and xenograft tumorigenesis by enhancing c-Myc/cyclinD1 and EMT signaling and by suppressing the caspase-dependent apoptosis pathway. Ketone body treatment reduced the proliferation- and migration-promoting effects of HMGCS2 knockdown in cells. In contrast, HMGCS2 overexpression increased the intracellular ketone level and inhibited cell proliferation, cell migration, and xenograft tumorigenesis. Finally, ketogenic diet administration significantly inhibited liver cancer cell growth in mice. Our studies highlight the potential therapeutic strategy of targeting HMGCS2-mediated ketogenesis in liver cancer.

| S-EPMC6966636 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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