Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pinin Induces Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma by Regulating m6A Modification.

ABSTRACT: Pinin is a moonlighting protein localized in desmosomes and nucleus. It could promote the growth of hepatocellular carcinoma. Whether this protein can induce epithelial-to-mesenchymal transition (EMT) and malignant progression in HCC is unknown. This work found that Pinin prompts EMT in vitro and in vivo. Further mechanism study found that Pinin increases the level of N6-methyladenosine (m6A) modification of RNA by interacting with METTL3, which in turn induces snail1 expression. These findings suggest that Pinin induces EMT by regulating m6A modification and, thus, could be a potential anticancer target for HCC therapy.

SUBMITTER: Qiao K

PROVIDER: S-EPMC8670902 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Pinin Induces Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma by Regulating m6A Modification.

Qiao Kailiang K Chen Caihong C Liu Haoyang H Qin Yuan Y Liu Huijuan H

Journal of oncology 20211207

Pinin is a moonlighting protein localized in desmosomes and nucleus. It could promote the growth of hepatocellular carcinoma. Whether this protein can induce epithelial-to-mesenchymal transition (EMT) and malignant progression in HCC is unknown. This work found that Pinin prompts EMT in vitro and in vivo. Further mechanism study found that Pinin increases the level of N6-methyladenosine (m6A) modification of RNA by interacting with <i>METTL3</i>, which in turn induces snail1 expression. These fi ...[more]

PMID: 34917148

Similar Datasets

Osteopontin promotes epithelial-mesenchymal transition of hepatocellular carcinoma through regulating vimentin.

Project description:Our previous studies have found that osteopontin (OPN) is a promoter for hepatocellular carcinoma (HCC) progression. However, the molecular mechanism by which OPN enhances HCC metastasis remains elusive. Epithelial-mesenchymal transition (EMT) of cancer cells plays a pivotal role in promoting metastatic process. In this study, we demonstrated that OPN promotes HCC metastasis by inducing an EMT-like, more aggressive cellular phenotype in vitro and in vivo. Furthermore, OPN was identified to interact with vimentin by reciprocal OPN and vimentin immunoprecipitation as well as co-immunofluorescence examination. By using deletion mutants, we found that the residues between 246 and 406 in vimentin are required for binding to OPN. Importantly, OPN significantly increased vimentin stability through inhibition of its protein degradation. Knockdown of vimentin neutralized the EMT induced by OPN both in vitro and in vivo. Moreover, a significant correlation between OPN and vimentin levels was found in clinical HCC specimens and their combination had a worse prognosis with shorter overall survival (OS) and time to recurrence (TTR). In multivariate analysis, OPN and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Collectively, this study indicates that OPN can induce EMT of HCC cells through increasing vimentin stability, which provides more in-depth understanding about the molecular mechanisms of OPN in promoting HCC metastasis and opens tantalizing therapeutic possibilities in HCC.

| S-EPMC4914337 | biostudies-literature

PTIP promotes recurrence and metastasis of hepatocellular carcinoma by regulating epithelial-mesenchymal transition.

Project description:Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide, which is mainly due to the high recurrence and metastasis rate after hepatectomy. In this study, we found that PTIP expression was dramatically upregulated in human HCC tissues and cell lines. High expression of PTIP was shown to be associated with aggressive clinicopathological features, including liver cirrhosis, vascular invasion and advanced stage. In addition, PTIP overexpression was independently associated with shorter survival and increased HCC recurrence in patients. Knockdown of the PTIP expression significantly inhibited invasion and metastasis in vitro and in vivo, whereas ectopic expression of PTIP significantly promoted invasion and metastasis. Mechanistically, PTIP promotes HCC progress by facilitating epithelial-mesenchymal transition (EMT). Notably, we also found that PTIP might increase miR-374a expression to promote EMT and metastasis in HCC. In summary, our study identified PTIP as a new potential prognostic indicator and therapeutic target for HCC.

| S-EPMC5601643 | biostudies-literature

Lysyl oxidase induces epithelial-mesenchymal transition and predicts intrahepatic metastasis of hepatocellular carcinoma.

Project description:Hepatocellular carcinoma (HCC) has high recurrence rates even after curative hepatectomy. Drug therapy for recurrence of HCC is still limited; therefore, identifying new therapeutic targets is urgently needed. We searched for genes that would predict HCC recurrence from intrahepatic metastasis in an exhaustive DNA microarray database by searching genes associated with high early recurrence rate and having higher expression in the tumor area compared to background liver. We detected lysyl oxidase (LOX) and validated the clinical significance of LOX in 358 patients who underwent hepatectomy. Expression of LOX was evaluated by qRT- PCR, and immunohistochemical (IHC) staining. High LOX expression group had a significantly higher recurrence rate than the low LOX expression group (2-year recurrence rate was 64.0% vs 24.2%, P < .0001 for IHC) and poorer survival rate (5-year rate was 60.1% vs 86.2%, P < .0001 for IHC). Multivariate analysis showed that high LOX expression was an independent risk factor for early recurrence (IHC: HR, 2.52; P < .0001). Bioinformatic analysis showed that LOX expression was associated with hypoxia-inducible factor-1α (HIF-1α) and the hypoxia cascade, suggesting that HIF-1α or hypoxia regulates LOX expression and induces epithelial-mesenchymal transition (EMT). In vitro, LOX and HIF-1α were involved in migration and invasion capability. High LOX expression is associated with EMT markers and predicts early recurrence and poor survival in patients with HCC. These findings indicate that lysyl oxidase could be a potential therapeutic target for early recurrence of HCC.

| S-EPMC6550133 | biostudies-literature

Bone morphogenetic protein-9 induces epithelial to mesenchymal transition in hepatocellular carcinoma cells.

Project description:Epithelial-mesenchymal transition (EMT) is an important mechanism to initiate cancer invasion and metastasis. Bone morphogenetic protein (BMP)-9 is a member of the transforming growth factor (TGF)-? superfamily. It has been suggested to play a role in cancer development in some non-hepatic tumors. In the present study, two hepatocellular carcinoma (HCC) lines, HLE and HepG2, were treated with BMP-9 in vitro, and phenotypic changes and cell motility were analyzed. In situ hybridization (ISH) and immunohistochemical analyses were performed with human HCC tissue samples in order to assess expression levels of BMP-9. In vivo, BMP-9 protein and mRNA were expressed in all the tested patients to diverse degrees. At the protein level, mildly positive (1 + ) BMP-9 staining could be observed in 25/41 (61%), and moderately to strongly positive (2 + ) in 16/41 (39%) of the patients. In 27/41 (65%) patients, the BMP-9 protein expression level was consistent with the mRNA expression level as measured by ISH. In those patients with 2 + protein level, nuclear pSmad1 expression in cancer cells was also significantly increased. Expression of BMP-9 was positively related to nuclear Snail expression and reversely correlated to cell surface E-cadherin expression, although this did not reach statistical significance. Expression levels of BMP-9 were significantly associated with the T stages of the investigated tumors and high levels of BMP-9 were detected by immunofluorescence especially at the tumor borders in samples from an HCC mouse model. In vitro, BMP-9 treatment caused a reduction of E-cadherin and ZO-1 and an induction of Vimentin and Snail expression. Furthermore, cell migration was enhanced by BMP-9 in both HCC cell lines. These results imply that EMT induced by BMP-9 is related to invasiveness of HCC.

| S-EPMC7657113 | biostudies-literature

FOXC1 contributes to microvascular invasion in primary hepatocellular carcinoma via regulating epithelial-mesenchymal transition.

Project description:The existence of microvascular invasion (MVI) formation is one of the most important risk factors predicting poor outcome in hepatocellular carcinoma (HCC) and its mechanism remains largely unknown. Epithelial-Mesenchymal Transition (EMT) has been suggested to be involved in many steps of the invasion-metastasis cascade. To elucidate the possible contribution of EMT to MVI, we initially evaluated the expression of 8 EMT-related transcription factors (TFs) in HCC patients with or without MVI and found that FOXC1 expression was significantly higher in patients with MVI than those without MVI (P < 0.05). Knockdown of FOXC1 expression in HCC cells resulted in a partial conversion of their EMT progresses, mainly regulating the mesenchymal component. Ectopic expression of snail, twist or TGF-?1 could induce expression of FOXC1, but none of the expression of snail, twist, slug or TGF-? was consistently down-regulated in response to FOXC1 silencing, suggesting FOXC1 might operate the downstream of other EMT regulators. In addition, knockdown of FOXC1 expression led to cytoskeleton modification accompanied by decreased ability of cell proliferation, migration, and invasion. Meanwhile, some matrix metalloproteinases (MMPs) and VEGF-A were also simultaneously down-regulated. Together, our findings demonstrate that FOXC1 is one of candidate predictive markers of MVI, and that inhibition of FOXC1 expression can partially reverse EMT program, offering a potential molecular therapeutic target for reducing tumor metastasis in HCC patients.

| S-EPMC3445051 | biostudies-literature

FAM134B induces tumorigenesis and epithelial-to-mesenchymal transition via Akt signaling in hepatocellular carcinoma.

Project description:Fam134b (JK-1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma. However, the roles of FAM134B during tumorigenesis of hepatocellular carcinoma (HCC) and in epithelial-to-mesenchymal transition (EMT) were previously unclear. In this study, we investigated the function of FAM134B in HCC and the related tumorigenesis mechanisms, as well as how FAM134B induces EMT. We detected the expression of FAM134B in a normal hepatic cell line, HCC cell lines, fresh specimens, and a HCC tissue microarray. A retrospective study of 122 paired HCC tissue microarrays was used to analyze the correlation between FAM134B and clinical features. Gain- and loss-of-function experiments, rescue experiments, Akt pathway activator/inhibitors, nude mice xenograft models, and nude mice lung metastasis models were used to determine the underlying mechanisms of FAM134B in inducing tumorigenesis and EMT in vitro and in vivo. The expression level of FAM134B was highly elevated in HCC, as compared with that in normal liver tissues and normal hepatic cells. Overexpression of FAM134B was significantly associated with tumor size (P = 0.025), pathological vascular invasion (P = 0.026), differentiation grade (P = 0.023), cancer recurrence (P = 0.044), and portal vein tumor thrombus (P = 0.036) in HCC. Patients with high expression of FAM134B had shorter overall survival and disease-free survival than patients with non-high expression of FAM134B. Furthermore, knockdown of FAM134B with shRNAs inhibited cell growth and motility, as well as tumor formation and metastasis in nude mice, all of which were promoted by overexpression of FAM134B. Our study demonstrated that Fam134b is an oncogene that plays a crucial role in HCC via the Akt signaling pathway with subsequent glycogen synthase kinase-3β phosphorylation, accumulation of β-catenin, and stabilization of Snail, which promotes tumorigenesis, EMT, and tumor metastasis in HCC.

| S-EPMC6441892 | biostudies-literature

MTF2 Induces Epithelial-Mesenchymal Transition and Progression of Hepatocellular Carcinoma by Transcriptionally Activating Snail.

Project description:Background:Metal regulatory transcription factor 2 (MTF2) has been previously reported as a protein binding to the metal response element of the mouse metallothionein promoter, which is involved in chromosome inactivation and pluripotency. However, the function of MTF2 in tumor formation and progression has not yet been completely elucidated. Methods:The expression of MTF2 and clinicopathological characteristics were evaluated by hepatocellular carcinoma (HCC) tissue microarray of 240 specimens. The role of MTF2 on HCC progression was determined using MTT, crystal violet, and transwell assays. Tumor growth was monitored in a xenograft model, and intrahepatic metastasis models were established. Results:The expression of MTF2 was increased in HCC and strongly associated with the clinical characteristics and prognosis. Forced expression of MTF2 in HCC cells significantly promoted cell growth, migration, and invasion in vitro. In contrast, downregulation of MTF2 inhibited cell growth, migration, and invasion in vitro. Moreover, knock down of MTF2 suppressed tumorigenesis and intrahepatic metastasis of HCC cells in vivo. Mechanistically, MTF2 overexpression may promote growth and epithelial-mesenchymal transition processes of HCC cells by facilitating Snail transcription. Conclusion:MTF2 promotes the proliferation, migration, and invasion of HCC cells by regulating Snail transcription, providing a potential therapeutic candidate for patients with HCC.

| S-EPMC6927270 | biostudies-literature

linc‑ROR facilitates hepatocellular carcinoma resistance to doxorubicin by regulating TWIST1‑mediated epithelial‑mesenchymal transition.

Project description:Long non‑coding RNAs are associated with cancer progression. Long intergenic non‑protein coding RNA (linc)‑regulator of reprogramming (ROR) enhances tumor development in hepatocellular carcinoma (HCC). However, the effect of chemoresistance and its underlying mechanisms in HCC are not completely understood. The present study aimed to identify the effect of ROR on sensitivity to doxorubicin (DOX) in HCC cells. In the present study, Cell Counting Kit‑8 and EdU assays were performed to assess cell viability and proliferation, respectively. In addition, E‑cadherin and vimentin protein expression levels were assessed via western blotting and immunofluorescence.The results of the present study demonstrated that HCC cells with high linc‑ROR expression levels were more resistant to DOX, and linc‑ROR knockdown increased HCC cell DOX sensitivity compared with the control group. The results indicated that compared with the NC siRNA group, linc‑ROR knockdown notably suppressed epithelial‑mesenchymal transition by downregulating twist family bHLH transcription factor 1 (TWIST1) expression. TWIST1 knockdown displayed a similar effect on HCC cell DOX sensitivity to linc‑ROR knockdown. Moreover, linc‑ROR knockdown‑induced HCC cell DOX sensitivity was inhibited by TWIST1 overexpression. The present study provided evidence that linc‑ROR promoted HCC resistance to DOX by inducing EMT via interacting with TWIST1. Therefore, linc‑ROR might serve as a therapeutic target for reducing DOX resistance in HCC.

| S-EPMC7974311 | biostudies-literature

Cetylpyridinium chloride inhibits hepatocellular carcinoma growth and metastasis through regulating epithelial-mesenchymal transition and apoptosis.

Project description:Hepatocellular carcinoma (HCC) is characterized by a lack of obvious clinical features in the early stages and is likely to progress to advanced HCC. Advanced HCC is a highly malignant tumor. However, there are few treatment options for advanced HCC. Therefore, screening for new drugs that target HCC will provide a new approach to the treatment of HCC. The CCK8 assay was performed to screen compounds inhibiting HCC cell proliferation and to evaluate the IC50 (half-maximal inhibitory concentration) of compounds on cell lines. Colony formation assay was used to determine HCC cell proliferation. The effect of compounds on HCC cell migration and invasion were analyzed using wound healing and transwell assays, respectively. Tumor growth and metastasis were assessed in vivo in a xenograft mouse model. Flow cytometry was carried out to measure apoptotic cells. Reverse transcription and quantitative real-time polymerase chain reaction (RT‒qPCR) and Western blot were performed to examine the expression of epithelial-mesenchymal transition (EMT)- and apoptosis-related genes. Through large-scale screening, we have discovered the anti-tumor activity of cetylpyridinium chloride (CPC) against HCC cells. CPC inhibited the proliferation, invasion and metastasis of HCC cells. Cancer cells are more sensitive to CPC than normal cells. CPC suppressed HCC tumor growth and metastasis in vivo. Mechanistically, CPC promoted apoptosis of HCC cells by affecting the expression of apoptosis-related genes, and inhibited HCC invasion and metastasis by suppressing EMT and expression of EMT markers. Our investigation showed that CPC significantly inhibited HCC cell proliferation, invasion and metastasis in vivo and in vitro, by inducing the expression of apoptosis-related genes and inhibiting expression of EMT markers, suggesting that CPC is a potential agent for HCC treatment.

| S-EPMC11414990 | biostudies-literature

METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition.

Project description:Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration (nAMD). Myofibroblasts originated from retinal pigment epithelial (RPE) cells through epithelial-mesenchymal transition (EMT) contribute to the fibrosis formation. N6-Methyladenosine (m6A) modification has been implicated in the EMT process and multiple fibrotic diseases. The role of m6A modification in EMT-related subretinal fibrosis has not yet been elucidated. In this study, we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization, METTL3 was upregulated in RPE cells. Through m6A epitranscriptomic microarray and further verification, high-mobility group AT-hook 2 (HMGA2) was identified as the key downstream target of METTL3, subsequently activating potent EMT-inducing transcription factor SNAIL. Finally, by subretinal injections of adeno-associated virus vectors, we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo. In conclusion, our present research identified an epigenetic mechanism of METTL3-m6A-HMGA2 in subretinal fibrosis and EMT of RPE cells, providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.

| S-EPMC10603769 | 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