Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LncRNA GATA6-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer via Repressing microRNA-543 to Up-Regulating RKIP

ABSTRACT: Background Much evidence unveils the significance of long non-coding RNAs (lncRNAs) in diverse cancers. This study was designed to clarify the function and mechanism of lncRNA GATA6 antisense RNA 1 (GATA6-AS1) in the progression of non-small cell lung cancer (NSCLC). Methods GATA6-AS1, miR-543 and Raf kinase inhibitor protein (RKIP) mRNA expressions were detected by qRT-PCR. Chi-square test was adopted to analyze the relationship between GATA6-AS1 expression and the clinicopathological parameters of NSCLC patients. NSCLC cells H1299 and H460 cells were used as overexpression or knockdown models, respectively, and cell proliferation and metastasis were determined by CCK-8 and Transwell assays. RKIP, E-cadherin, N-cadherin, STAT3, p-STAT3 expressions in NSCLC cells were detected by Western blot. The targeting relationship between GATA6-AS1 and miR-543 was confirmed by dual-luciferase reporter assay. Results GATA6-AS1 was significantly lowly expressed in NSCLC tissues and cell lines, and its low expression level was significantly correlated with larger tumor size and positive lymph node metastasis. GATA6-AS1 overexpression inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition of NSCLC cells, while GATA6-AS1 knockdown caused the opposite effects. Mechanistically, it was confirmed that GATA6-AS1 impeded NSCLC cell proliferation and metastasis by adsorbing miR-543 and up-regulating the expression of RKIP. Conclusions As a tumor suppressor, GATA6-AS1 participates in suppressing the progression of NSCLC by modulating the miR-543/RKIP axis.

SUBMITTER: Gong Z

PROVIDER: S-EPMC7532887 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Long non-coding RNA (lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating leucine zipper tumor suppressor (LZTS3) through sponging microRNA miR-1275.

Project description:It is necessary to explore new molecules for the improvement of precise diagnosis and antitumor therapies in lung cancer. LncRNAs (long non-coding RNAs) play an important role in the regulation of cancer cell malignant behavior and tumor development. In this work, we found that a newly discovered lncRNA, lncRNA PGM5P4-AS1, was lower expressed in lung cancer tissues than adjacent tissues. Then, the lncRNA PGM5P4-AS1 was overexpressed or knocked-down in different lung cancer cells, and its effects on the malignant phenotypes were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, wound healing assay, and transwell assay. The results showed that the overexpression of PGM5P4-AS1 inhibited lung cancer cell proliferation, migration, and invasion activities, while these abilities were prominently promoted by the interference of PGM5P4-AS1. Further, the growth of lung cancer tumors in nude mice was also inhibited by PGM5P4-AS1 overexpression. In mechanism, PGM5P4-AS1 has the binding site of miR-1275 and could positively regulate the expression of LZTS3 via sponging miR-1275. In conclusion, PGM5P4-AS1 could be a potential precise diagnosis and therapeutic target biomarker of lung cancer.

| S-EPMC8806334 | biostudies-literature

Overexpressed lncRNA GATA6-AS1 Inhibits LNM and EMT via FZD4 through the Wnt/?-Catenin Signaling Pathway in GC.

Project description:Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Accumulating evidence reveals the significance of long non-coding RNAs (lncRNAs) in various cancers. The current study aimed to evaluate the role of GATA6 antisense RNA 1 (GATA6-AS1) in the epithelial-mesenchymal transition (EMT) and lymph node metastasis (LNM) in GC. GC-related microarray datasets were initially retrieved from the GEO with differentially expressed lncRNAs screened, followed by evaluation of the regulatory relationship between Frizzled 4 (FZD4) and GATA6-AS1. The detailed regulatory mechanism by which GATA6-AS1 influences the Wnt/?-catenin signaling pathway and GC cell biological behaviors was investigated by treating SGC7901 cells with overexpressed GATA6-AS1, specific antisense oligonucleotide against GATA6-AS1, and lithium chloride (LiCl; activator of the Wnt/?-catenin signaling pathway). Finally, xenograft nude mice were used to assay tumor growth and LNM in vivo. GATA6-AS1 was poorly expressed, but FZD4 was highly expressed in GC tissues and cells. Elevated GATA6-AS1 reduced FZD4 expression by recruiting enhancer of zeste homolog 2 (EZH2) and trimethylation at lysine 27 of histone H3 (H3K27me3) to the FZD4 promoter region via the inactivated Wnt/?-catenin signaling pathway, whereby cell invasion, migration, and proliferation, tumor growth, and LNM in nude mice were reduced. Taken together, overexpressed GATA6-AS1 downregulated the expression of FZD4 to inactivate the Wnt/?-catenin signaling pathway, which ultimately inhibited GC progression.

| S-EPMC6976905 | biostudies-literature

Silenced lncRNA DDX11-AS1 or up-regulated microRNA-34a-3p inhibits malignant phenotypes of hepatocellular carcinoma cells via suppression of TRAF5.

Project description:BackgroundStudies have discussed long noncoding RNA DDX11-AS1 (DDX11-AS1)-mediated downstream mechanism in hepatocellular carcinoma (HCC). The goal of this study was to investigate the regulatory mechanism of DDX11-AS1-mediated microRNA-34a-3p (miR-34a-3p)/tumor necrosis factor receptor-associated factor 5 (TRAF5) axis on HCC cells.MethodsDDX11-AS1, miR-34a-3p and TRAF5 expression levels in HCC were detected. The correlation of DDX11-AS1, miR-34a-3p and TRAF5 in HCC patients was analyzed by Pearson test. HCC cells were transfected with corresponding plasmid/oligonucleotide, and cell proliferation, migration, invasion, apoptosis and tumor formation ability were detected. Bioinformatics software, dual luciferase report experiment and RNA-pull down experiment analysis were applied to verify the targeting relationship between DDX11-AS1, miR-34a-3p and TRAF5.ResultsElevated DDX11-AS1 and TRAF5 and reduced miR-34a-3p exhibited in HCC. Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibited the proliferation, migration, invasion, promoted apoptosis of HCC cells and repressed the tumor growth in nude mice. In addition, DDX11-AS1 bound to miR-34a-3p to target TRAF5. Silencing TRAF5 or elevating miR-34a-3p expression mitigated up-regulated DDX11-AS1-mediated promotion of tumor growth.ConclusionSilenced DDX11-AS1 or up-regulated miR-34a-3p inhibits HCC cell growth via elevation of TRAF5, which could be of great benefit to find early diagnostic markers for HCC patients.

| S-EPMC7983398 | biostudies-literature

lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1.

Project description:Glucose metabolism reprogramming is one of the hallmarks of cancer cells, although functional and regulatory mechanisms of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remain incompletely understood. The aim of this study was to uncover the role of GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD. We discovered that overexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolism-related assays revealed that GAS6-AS1 inhibited glucose metabolism reprogramming. Mechanically, GAS6-AS1 was found to repress the expression of glucose transporter GLUT1, a key regulator of glucose metabolism. Ectopic expression of GLUT1 restored the inhibition effect of GAS6-AS1 on cancer progression and glucose metabolism reprogramming. Further investigation identified that GAS6-AS1 directly interacted with transcription factor E2F1 and suppressed E2F1-mediated transcription of GLUT1, and GAS6-AS1 was downregulated in LUAD tissues and correlated with clinicopathological characteristics and survival of patients. Taken together, our results identified GAS6-AS1 as a novel tumor suppressor in LUAD and unraveled its underlying molecular mechanism in reprogramming glucose metabolism. GAS6-AS1 potentially may serve as a prognostic marker and therapeutic target in LUAD.

| S-EPMC8181633 | biostudies-literature

GATA6-AS1 via Sponging miR-543 to Regulate PTEN/AKT Signaling Axis Suppresses Cell Proliferation and Migration in Gastric Cancer.

Project description:Gastric cancer (GC) is one of the most common and lethal cancers worldwide. In view of the prominent roles of long noncoding RNAs (lncRNAs) in cancers, we investigated the specific role and underlying mechanism of GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in GC. Quantitative real-time polymerase chain reaction (qRT-PCR) detected GATA6-AS1 expression in GC cell lines. Functional assays were conducted to explore the role of GATA6-AS1 in GC. Furthermore, mechanism investigations were implemented to uncover the interaction among GATA6-AS1, microRNA-543 (miR-543), and phosphatase and tensin homolog (PTEN). In the present study, it was found that GATA6-AS1 expression is significantly downregulated in GC cell lines. Functionally, GATA6-AS1 markedly suppresses GC cell growth and migration in vitro and in vivo tumorigenesis. Besides tumor suppressor, GATA6-AS1 serves as a miR-543 sponge. Specifically speaking, GATA6-AS1 acts as a competing endogenous RNA (ceRNA) of miR-543 to upregulate the expression of PTEN, thus inactivating AKT signaling pathway to inhibit GC progression. In conclusion, this study has manifested that GATA6-AS1 inhibits GC cell proliferation and migration as a sponge of miR-543 by regulating PTEN/AKT signaling axis, offering new perspective into developing novel GC therapies.

| S-EPMC10238141 | biostudies-literature

Correction to: Silenced lncRNA DDX11-AS1 or up-regulated microRNA-34a-3p inhibits malignant phenotypes of hepatocellular carcinoma cells via suppression of TRAF5.

Project description: Not available

| S-EPMC8662869 | biostudies-literature

LncRNA ZEB1-AS1 inhibits renal fibrosis in diabetic nephropathy by regulating the miR-217/MAFB axis.

Project description:Diabetic nephropathy (DN) is a common chronic microvascular complication of diabetes, characterized by the deposition of extracellular matrix (ECM) proteins. Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has been implicated in kidney fibrosis of human DN. Here, we further explored the detailed molecular mechanism of ZEB1-AS1 in renal fibrosis in DN. The expression of ZEB1-AS1 was monitored using a quantitative real-time polymerase chain reaction. Blood glucose concentrations of mice were measured using a fast blood glucose meter. The high-performance liquid chromatography method was used to measure the serum creatinine level. Western blot analysis was used to detect the protein level of α-smooth muscle actin (α-SMA), fibronectin, collagen I, collagen IV and MAFB. The level of urine albumin was detected using the BCG (Bromocresol Green) albumin assay kit. The interaction between ZEB1-AS1, miR-217 and MAFB was investigated via the luciferase reporter and RNA immunoprecipitation analysis. Decreased ZEB1-AS1 expression in DN patients and db/db diabetic mice as well as in high glucose (HG)-induced HK-2 cells was detected. Reduction in the α-SMA, fibronectin, collagen I and IV protein expression, induced by the overexpressed ZEB1-AS1, was found in db/db diabetic mice and HG-induced HK-2 cells. In addition, we discovered that ZEB1-AS1 directly targeted miR-217, and MAFB was the target of miR-217; thus, ZEB1-AS1 might regulate the MAFB expression by targeting miR-217. Furthermore, functional experiments indicated that overexpressed ZEB1-AS1 might have decreased the accumulation of ECM proteins in the HG-induced HK-2 cells by regulating the miR-217 and MAFB expression. Overexpressed ZEB1-AS1 may inhibit renal fibrosis in diabetic nephropathy by regulating the miR-217/MAFB axis, identifying novel therapeutic targets for renal fibrosis in diabetic nephropathy.

| S-EPMC9088285 | biostudies-literature

MicroRNA-543 controls pancreatic cancer development by LINC00847-microRNA-543-STK31 axis

Project description:Background Pancreatic cancer (PC) is one of the most malignant cancers of the gastrointestinal tract. However, the study of targeted therapy research in PC is not very thorough. Therefore, targeted molecular markers are needed to aid in the diagnosis and treatment of PC. Methods In our research, we investigated the biological functions and molecular mechanism of microRNA-543 in PC. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to analyze the transcription and protein expression of microRNA-543, Serine/threonine kinase 31 (STK31), and LINC00847 in BxPC-3 and PANC-1 cells. Subsequently, Cell Counting Kit-8 (CCK-8), Transwell, colony formation, and flow cytometry (FCM) assays were utilized to evaluate cell growth, migration, invasion, and apoptosis. WB and fluorescence in-situ hybridization (FISH) were used to evaluate the epithelial-mesenchymal transition (EMT) process and subcellular localization. RNA immunoprecipitation (RIP), double luciferase reporter, and RNA-pull down assays were performed to determine the targeting relationship between microRNA-543 and STK31 or microRNA-543 and LINC00847. Results While microRNA-543 expression was discovered to be low in PC, LINC00847 and STK31 were overexpressed at significant levels. MicroRNA-543 knockdown dramatically increased PC cell growth, invasion, metastasis, and EMT, as well as decreased apoptosis in functional studies. Furthermore, microRNA-543 and STK31 were found to be mutual targets. LINC00847 acted as a molecular sponge for microRNA-543 and a competitive endogenous RNA (ceRNA) for STK31, thereby increasing STK-31 transcription. Conclusions Our results suggest that microRNA-543, through the LINC00847/microRNA-543/STK31 axis, plays a role in the development of PC as a tumor suppressor. As a result, microRNA-543 may prove to be an effective diagnostic and therapeutic target for PC.

| S-EPMC9830362 | biostudies-literature

GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation.

Project description:Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation, but how lncRNA is integrated with known transcriptional regulatory network is poorly understood. Here, we utilize human definitive endoderm differentiation as a model system and decipher the functional interaction between lncRNA and key transcriptional factor. We have identified GATA6-AS1, an lncRNA divergently transcribed from the GATA6 locus, is highly expressed during endoderm differentiation. Knockdown of GATA6-AS1 in human pluripotent stem cells has no influence on morphology and pluripotency; however, GATA6-AS1 depletion causes the deficiency of definitive endoderm differentiation. GATA6-AS1 positively regulates the expression of endoderm key factor GATA6. Further investigation shows GATA6-AS1 interacts with SMAD2/3 and activates the transcription of GATA6. In addition, overexpression of GATA6 is able to rescue the defect of endoderm differentiation due to the absence of GATA6-AS1, suggesting that GATA6 is the functional target of GATA6-AS1 during endoderm differentiation. Ultimately, our study reveals that GATA6-AS1 is necessary for human endoderm specification and reveals the underlying mechanism between GATA6-AS1 and GATA6.

| S-EPMC7486217 | biostudies-literature

Emodin inhibits pancreatic cancer EMT and invasion by up?regulating microRNA?1271.

Project description:Emodin has a direct inhibitory effect on the growth and metastasis of a variety of malignant tumor cells. MicroRNA?1271 (miR?1271) has an extensive tumor?suppression effect by inhibiting epithelial mesenchymal transition (EMT) in tumor cells and induces tumor cell apoptosis. Proceeding with the EMT regulatory mechanism of pancreatic carcinoma, the present study aimed to examine the inhibitory effect of miR?1271 and emodin against invasion and metastasis of pancreatic carcinoma. The expression of EMT?related markers (E?cadherin, ZEB1 and TWIST1) was analyzed by western blotting. mRNA levels of miR?1271, E?cadherin, ZEB1 and TWIST1 in pancreatic tumor cells (SW1990) were measured through reverse transcription?quantitative polymerase chain reaction and cell invasiveness was detected using Transwell assays. In addition, a liver metastatic model was established with an implantation of pancreatic tumor tissue into the spleens of nude mice to study the effect of emodin on pancreatic cancer liver metastasis. In the present study, it was demonstrated that miR?1271 significantly decreased in pancreatic cancer cells and tissues. Twist1 may be a target gene of miR?1271. Emodin could inhibit the proliferation ability of pancreatic cancer cells and increased miR?1271 expression level. Further, we found that miR?1271 significantly inhibited SW1990 cell EMT and invasive ability. We also provided the evidence that emodin inhibited SW1990 cell EMT by raising the level of miR?1271. Moreover, the in vivo experiments have verified the inhibiting effect of emodin against liver metastasis of pancreatic cancer. The data in the present study indicated that emodin inhibited pancreatic cancer EMT and invasion by increasing the content of miR?1271.

| S-EPMC6102704 | 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