Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-catenin via Ezh2.

ABSTRACT: Evidences have shown that lncRNAs involve in the initiation and progression of various cancers including esophageal squamous cell carcinoma (ESCC). The aberrant expression of lncRNA MALAT1 was investigated in 106 paired ESCC tissues and adjacent non-cancerous tissues by qRT-PCR. Down-regulated MALAT1 and Ezh2 over-expression plasmid were constructed respectively to analyze the expression of β-catenin, Lin28 and Ezh2 genes. We found that the MALAT1 expression level was higher in human ESCC tissues (P=0.0011), which was closely correlated with WHO grade (P=0.0395, P=0.0331), lymph node metastasis (P=0.0213) and prognosis (P=0.0294). Silencing of MALAT1 expression inhibited cell proliferation, migration and tumor sphere formation, while increasing cell apoptosis of esophageal cancer in vitro. Down-regulation of MALAT1 decreased the expression of β-catenin, Lin28 and Ezh2 genes, while over-expressed Ezh2 combined with MALAT1 down-regulation completely reversed the si-MALAT1-mediated repression of β-catenin and Lin28 in esophageal cancer cells. Animal experiments showed that knockdown of MALAT1 decreased tumor formation and improved survival. MALAT1 promotes the initiation and progression of ESCC, suggesting that inhibition of MALAT1 might be a potential target for treatment of ESCC.

SUBMITTER: Wang W

PROVIDER: S-EPMC5041935 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway.

Project description:The RNA binding protein TRA2A, a member of the transformer 2 homolog family, plays a crucial role in the alternative splicing of pre-mRNA. However, it remains unclear whether TRA2A is involved in non-coding RNA regulation and, if so, what are the functional consequences. By analyzing expression profiling data, we found that TRA2A is highly expressed in esophageal cancer and is associated with disease-free survival and overall survival time. Subsequent gain- and loss-of-function studies demonstrated that TRA2A promotes proliferation and migration of esophageal squamous cell carcinoma and adenocarcinoma cells. RNA immunoprecipitation and RNA pull-down assay indicated that TRA2A can directly bind specific sites on MALAT1 in cells. In addition, ectopic expression or depletion of TRA2A leads to MALAT expression changes accordingly, thus modulates EZH2/β-catenin pathway. Together, these findings elucidated that TRA2A triggers carcinogenesis via MALAT1 mediated EZH2/β-catenin axis in esophageal cancer cells.

| S-EPMC8247389 | biostudies-literature

Glyoxalase 1, regulated by LncRNA MALAT1, promotes malignant development of esophageal squamous cell carcinoma.

Project description:In previous study we found that long noncoding RNA (lncRNA) MALAT1 promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC), and that the following microarray chip screening of MALAT1 target genes showed that Glyoxalase I (GLO1) was a potential downstream effector of MALAT1. In this study, we further confirmed that GLO1 was regulated by MALAT1. GLO1 belongs to the glyoxalase system, which encodes a ubiquitous detoxification pathway being implicated in the progression of multiple malignancies. However, currently, the role of GLO1 in human ESCC remains unclear. To explore the clinical significance of GLO1 in ESCC, we first determined the expression of GLO1 in 40 paired ESCC tissues and adjacent normal tissues. We found that the expression level of GLO1 was higher in human ESCC tissues (P=0.0040). Knockdown of GLO1 by siRNA significantly inhibited the proliferation and migration of ESCC cells. In vivo assays showed that knockdown of GLO1 decreased tumor growth. Overall, GLO1 might be an essential effector of lncRNA MALAT1 which promotes ESCC progression and can be identified as a potential therapeutic target for ESCC in the future.

| S-EPMC6958265 | biostudies-literature

Long noncoding RNA XIST promotes malignancies of esophageal squamous cell carcinoma via regulation of miR-101/EZH2.

Project description:The long non-coding RNA XIST is a long non-coding RNA that associates with polycomb repressive complex 2 to regulate X-chromosome inactivation in female mammals. The biological roles as well as the underlying mechanisms of XIST in esophageal squamous cell carcinoma remained yet to be solved. Our data indicated that XIST was significantly upregulated in esophageal squamous cancerous tissues and cancer cell lines, as compared with that in the corresponding non-cancerous tissues and immortalized normal squamous epithelial cells. High XIST expression predicted poor prognosis of esophageal squamous cancer patients. Lentivirus mediated knockdown of XIST inhibited proliferation, migration and invasion of esophageal squamous cancer cells in vitro and suppressed tumor growth in vivo. Knockdown of XIST resulted in elevated expression of miR-101 and decreased expression of EZH2. Further analysis showed that XIST functioned as the competitive endogenous RNA of miR-101 to regulate EZH2 expression. Moreover, enforced expression of EZH2 significantly attenuated the anti-proliferation activity upon XIST knockdown. Conclusively, XIST plays an important role in malignant progression of ESCC via modulation of miR-101/EZH2 axis.

| S-EPMC5652682 | biostudies-literature

Aurora-A enhances malignant development of esophageal squamous cell carcinoma (ESCC) by phosphorylating β-catenin.

Project description:The Aurora-A gene encodes a serine/threonine protein kinase that is frequently overexpressed in several types of human tumors. The overexpression of Aurora-A has been observed to associate with the grades of differentiation, invasive capability and distant lymph node metastasis of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism by which Aurora-A promotes malignant development of ESCC is still largely unknown. In this study, we show that Aurora-A overexpression enhances tumor cell invasion and metastatic potential in vitro and in vivo. Furthermore, Aurora-A overexpression inhibits the degradation of β-catenin, promotes its dissociation from cell-cell contacts and increases its nuclear translocation. We also demonstrate for the first time that Aurora-A directly interacts with β-catenin and phosphorylates β-catenin at Ser552 and Ser675. Substitutions of serine residue with alanine at single or both positions substantially attenuate Aurora-A-mediated stabilization of β-catenin, abolish its cytosolic and nuclear localization as well as transcriptional activity. In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic β-catenin expression in ESCC tissues. In view of our results, we propose that Aurora-A-mediated phosphorylation of β-catenin is a novel mechanism of malignancy development of tumor.

| S-EPMC5528673 | biostudies-literature

Elevated DHODH expression promotes cell proliferation via stabilizing β-catenin in esophageal squamous cell carcinoma.

Project description:As a key enzyme in de novo pyrimidine biosynthesis, the expression level of dihydroorotate dehydrogenase (DHODH) has been reported to be elevated in various types of malignant tumors and its tumor-promoting effect was considered to relate to its pyrimidine synthesis function. Here, we revealed one intriguing potential mechanism that DHODH modulated β-catenin signaling in esophageal squamous cell carcinoma (ESCC). We demonstrated that DHODH directly bound to the NH2 terminal of β-catenin, thereby, interrupting the interaction of GSK3β with β-catenin and leading to the abrogation of β-catenin degradation and accumulation of β-catenin in the nucleus, which in turn, resulted in the activation of β-catenin downstream genes, including CCND1, E2F3, Nanog, and OCT4. We further demonstrated that the regulation of β-catenin by DHODH was independent of DHODH catalyzing activity. Univariate and multivariate analyses suggested that DHODH expression might be an independent prognostic factor for ESCC patients. Collectively, our study highlights the pivotal role of DHODH mediated β-catenin signaling and indicates that DHODH may act as a multi-functional switcher from catalyzing pyrimidine metabolism to regulating tumor-related signaling pathways in ESCC.

| S-EPMC7566478 | biostudies-literature

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205.

Project description:Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues, where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas ?-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial-mesenchymal transition via E-cadherin recovery and ?-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease.

| S-EPMC5884967 | biostudies-literature

circ-GSK3beta Promotes metastasis in esophageal squamous cell carcinoma by targeting GSK3beta to augment beta-catenin Signaling

Project description:Circular RNAs, a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. We found that CircGSK3beta exerts critical roles in promoting ESCC metastasis and may serve as an exploitable therapeutic target for patients with ESCC. The plasma level of circGSK3beta have promising potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.

2019-11-25 | GSE131969 | GEO

SAMD9 Promotes Postoperative Recurrence of Esophageal Squamous Cell Carcinoma by Stimulating MYH9-Mediated GSK3β/β-Catenin Signaling.

Project description:Recurrence is a challenge to survival after the initial treatment of esophageal squamous cell carcinoma (ESCC). But, its mechanism remains elusive and there are currently no biomarkers to predict postoperative recurrence. Here, the possibility of sterile alpha motif domain-containing protein 9 (SAMD9) as a predictor of postoperative recurrence of ESCC is evaluated and the molecular mechanisms by which SAMD9 promotes ESCC recurrence are elucidated. The authors found that the high level of SAMD9 is correlated with postoperative recurrence and poor prognosis of ESCC. Overexpression of SAMD9 promotes tumor stemness, angiogenesis, and EMT, while downregulation of SAMD9 reduced these phenotypes. Mechanistically, it is found that SAMD9 stimulated ubiquitination-mediated glycogen synthase kinase-3 beta (GSK-3β) degradation by interaction with myosin-9 (MYH9) and TNF receptor-associated factor 6 (TRAF6), which in turn activated Wnt/β-catenin pathway. Further, the authors demonstrated that silencing SAMD9 inhibited lung metastasis and tumor formation in vivo. Finally, the authors found that silencing MYH9 or β-catenin, or overexpressing GSK-3β inhibited SAMD9-stimulated ESCC cell stemness, EMT, angiogenesis, metastasis, and tumorigenicity. Together, the findings indicate that the SAMD9/MYH9/GSK3β/β-catenin axis promotes ESCC postoperative recurrence and that SAMD9 is a crucial target for ESCC therapy. Additionally, SAMD9 has the potential as a predictor of postoperative recurrence in ESCC.

| S-EPMC10104667 | biostudies-literature

TGF-β1-Induced Upregulation of MALAT1 Promotes Kazakh's Esophageal Squamous Cell Carcinoma Invasion by EMT.

Project description:Transforming growth factor β1 (TGF-β1) plays an important role in tumor initiation and development by inducing epithelial-mesenchymal Transition (EMT). Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is a long noncoding RNA (lncRNA) that contributes to the invasion and metastasis of tumors, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the underlying mechanisms implicated in EMT and to clarify whether TGF-β1 regulates MALAT1 expression, thereby promoting the invasion of ESCC. Expression of TGF-β1, MALAT1 and EMT-related markers, including E-cadherin and Vimentin, was detected in clinical samples of Kazakh's ESCC. The role of TGF-β1 in the regulation of MALAT1 in ESCC invasion was evaluated at the ESCC cell line level. High TGF-β1 expression was significantly associated with poor survival among patients with Kazakh's ESCC. Additionally, the expression of Vimentin was upregulated, and the expression of E-cadherin was downregulated and varied. The expression of MALAT1 positively correlated with the expression of TGF-β1 both in vivo and in vitro. Furthermore, knockdown of MALAT1 inhibited TGF-β1-induced EMT. Our data indicate that MALAT1 is heavily involved in EMT induced by TGF-β1. MALAT1 may be a therapeutic target in the suppression of metastasis and invasion of ESCC.

| S-EPMC7592017 | biostudies-literature

circGSK3? promotes metastasis in esophageal squamous cell carcinoma by augmenting ?-catenin signaling.

Project description:BACKGROUND:Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. METHODS:Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3?) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3?, and the detection rates of plasma circGSK3? for ESCC were investigated. RESULTS:We demonstrated that upregulated expression of circGSK3? was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3? promoted ESCC cell migration and invasion via direct interaction with GSK3? and inhibiting GSK3? activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3? expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively. CONCLUSIONS:CircGSK3? exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3? have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.

| S-EPMC6854808 | 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