Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR-21-5p/CASKIN1/cAMP Axis

ABSTRACT: Glioma is a type of malignant intracranial tumor. Extensive research has identified the participation of long noncoding RNAs (lncRNAs) in glioma progression. This study investigated the mechanism of LINC00294 in mitochondrial function and glioma cell apoptosis. Glioma miRNA and mRNA microarray datasets were obtained, and differentially expressed lncRNAs in glioma were screened through various databases. The LINC00294 expression in glioma patients and glioma cells was detected. Glioma cells were treated under hypoxic conditions and transfected with LINC00294 silencing. The apoptosis and mitochondrial function of glioma cells were measured. The expressions of and relations among miR-21-5p, CASKIN1, and cAMP in glioma cells were analyzed. Under hypoxic conditions and LINC00294 silencing, the apoptosis and mitochondrial function of glioma cells were detected after inhibiting miR-21-5p or overexpressing CASKIN1. Our results indicated that LINC00294 was downregulated in glioma. LINC00294 silencing inhibited glioma cell apoptosis under hypoxia. LINC00294 silencing reversed the inhibition of hypoxia on mitochondrial function under hypoxia. LINC00294 promoted the CASKIN1 expression by sponging miR-21-5p and activated the cAMP pathway. Inhibition of miR-21-5p or overexpression of CASKIN1 annulled the effects of LINC00294 silencing on mitochondrial function and glioma cell apoptosis under hypoxia. In conclusion, LINC00294 elevated the CASKIN1 expression by sponging miR-21-5p and activating the cAMP signaling pathway, thus inhibiting mitochondrial function and facilitating glioma cell apoptosis.

SUBMITTER: Dong X

PROVIDER: S-EPMC8580631 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis.

Project description:Prostaglandin-E1 (PGE1) is a potent vasodilator with anti-inflammatory and antiplatelet effects. However, the mechanism by which PGE1 contributes to the amelioration of cardiac injury remains unclear. The present study was designed to investigate how PGE1 protects against hypoxia/reoxygenation (H/R)-induced injuries by regulating microRNA-21-5p (miR-21-5p) and fas ligand (FASLG). Rat H9C2 cells and isolated primary cardiomyocytes were cultured under hypoxic conditions for 6 h (6H, hypoxia for 6 h), and reoxygenated for periods of 6 (6R, reoxygenation for 6 h), 12, and 24 h, respectively. Cells from the 6H/6R group were treated with various doses of PGE1; after which, their levels of viability and apoptosis were detected. The 6H/6R treatment regimen induced the maximum level of H9C2 cell apoptosis, which was accompanied by the highest levels of Bcl-2-associated X protein (Bax) and cleaved-caspase-3 expression and the lowest level of B-cell lymphoma 2 (Bcl-2) expression. Treatment with PGE1 significantly diminished the cell cytotoxicity and apoptosis induced by the 6H/6R regimen, and also decreased expression of IL-2, IL-6, P-p65, TNF-α, and cleaved-caspase-3. In addition, we proved that PGE1 up-regulated miR-21-5p expression in rat cardiomyocytes exposed to conditions that produce H/R injury. FASLG was a direct target of miR-21-5p, and PGE1 reduced the ability of H/R-injured rat cardiomyocytes to undergo apoptosis by affecting the miR-21-5p/FASLG axis. In addition, we proved that PGE1 could protect primary cardiomyocytes against H/R-induced injuries. These results indicate that PGE1 exerts cardioprotective effects in H9C2 cells during H/R by regulating the miR-21-5p/FASLG axis.

| S-EPMC6923339 | biostudies-literature

Silencing lncRNA FOXD2-AS1 inhibits proliferation, migration, invasion and drug resistance of drug-resistant glioma cells and promotes their apoptosis via microRNA-98-5p/CPEB4 axis.

Project description:OBJECTIVE:This study was conducted to elucidate the long non-coding RNA FOXD2-AS1 (lncRNA FOXD2-AS1) expression in glioma and its mechanism on the biological features of glioma cells and the drug resistance of temozolomide (TMZ). RESULTS:Highly expressed FOXD2-AS1 was found in glioma. There was more powerful chemotherapeutic resistance of TMZ resistant cell lines than that of the parent cell lines. Silence of FOXD2-AS1 suppressed proliferation and drug resistance and promoted apoptosis of drug-resistant glioma cells. Overexpressed FOXD2-AS1 presented an opposite trend. FOXD2-AS1 could be used as a competing endogenous RNA to adsorb miR-98-5p, thereby up-regulating CPEB4. CONCLUSION:Our study suggests that down-regulated FOXD2-AS1 repressed invasion, proliferation, migration and drug resistance of drug-resistant glioma cells while stimulating their apoptosis via increasing miR-98-5p and inhibiting CPEB4 expression. METHODS:FOXD2-AS1, microRNA-98-5p (miR-98-5p) and cytoplasmic polyadenylation element binding (CPEB4) expression in glioma tissues were tested. Expression of E-cadherin, N-cadherin and Vimentin in glioma cells were explored. A series of assays were conducted to detect the function of FOXD2-AS1 in migration, proliferation, apoptosis, and invasion of glioma cells. Changes in drug-resistance of cells under TMZ treatment were examined, and tumor formation in nude mice was performed to test the changes of drug resistance in vivo.

| S-EPMC6914387 | biostudies-literature

CircPOSTN/miR-361-5p/TPX2 axis regulates cell growth, apoptosis and aerobic glycolysis in glioma cells.

Project description:BackgroundGlioma is the most primary central nervous system tumor in adults. The 5 year survival rate for glioma patients remains poor, although treatment strategies had improved in the past few decades. The cumulative studies have shown that circular RNA (circRNA) is associated with glioma process, so the purpose of this study is to clarify the function of circPOSTN in glioma.MethodsThe expression levels of circPOSTN, miR-361-5p, and targeting protein for Xenopus kinesin-like protein 2 (TPX2) were assessed with real-time quantitative polymerase chain reaction (RT-qPCR). The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were executed to examine proliferation and apoptosis of glioma cells, respectively. Western blot was applied to assess protein expression. The glucose metabolism of glioma cells was analyzed by testing the glucose consumption, lactate production, ATP level, reactive oxygen species (ROS) accumulation and performing Seahorse XF assay. The interaction relationship between miR-361-5p and circPOSTN or TPX2 was analyzed by bioinformatics database and dual-luciferase reporter assay. The influences of circPOSTN silencing in vivo were observed by a xenograft experiment.ResultsCircPOSTN was overexpressed in glioma tissues and cells. Absence of circPOSTN in glioma cells promoted apoptosis while impeded proliferation and aerobic glycolysis, which were mitigated by silencing miR-361-5p. What's more, loss-of-functional experiment suggested that knockdown of TPX2 repressed proliferation and aerobic glycolysis, while induced apoptosis in glioma cells. In addition, circPOSTN targetedly regulated TPX2 expression in glioma cells via sponging miR-361-5p. In vivo study revealed that deficiency of circPOSTN restrained tumor growth.ConclusionMechanistically, circPOSTN regulated cell growth, apoptosis, and aerobic glycolysis in glioma through miR-361-5p/TPX2 axis.

| S-EPMC7409503 | biostudies-literature

The MFF-SIRT1/3 axis, regulated by miR-340-5p, restores mitochondrial homeostasis of hypoxia-induced pulmonary artery smooth muscle cells.

Project description:Mitochondrial dynamics and quality control play a central role in the maintenance of the proliferation-apoptosis balance, which is closely related to the progression of pulmonary arterial hypertension (PAH). However, the exact mechanism of this balance remains unknown. Pulmonary artery smooth muscle cells (PASMCs) were cultured in hypoxia condition for constructing a PAH model in vitro. The expression of genes and proteins were determined by qRT-PCR and western bolt assays. Cell proliferation-apoptosis balance were tested by MTT, EdU and TUNEL assays. The mitochondrial functions were assessed by flow cytometry, JC-1, Mito tracker red staining, and corresponding kits. Besides, the molecular interaction was validated by dual-luciferase reporter assay. MFF was overexpressed in hypoxia-treated PAMSCs. Knockdown of MFF significantly repressed the excessive proliferation but enhanced cell apoptosis in hypoxia-treated PAMSCs. Moreover, MFF silencing improved mitochondrial function of hypoxia-treated PAMSCs by increasing ATP production and decreasing ROS release and mitochondrial fission. Mechanistically, MFF was a directly target of miR-340-5p, and could negatively regulate SIRT1/3 expression. Subsequently, functional rescue assays showed that the biological effects of MFF in hypoxia-treated PAMSCs were negatively regulated by miR-340-5p and depended on the regulation on SIRT1/3 pathway. These results provided evidences that miR-340-5p regulated MFF-SIRT1/3 axis to improve mitochondrial homeostasis and proliferation-apoptosis imbalance of hypoxia-treated PAMSCs, which provided a theoretical basis for the prevention and treatment of PAH.

| S-EPMC9042702 | biostudies-literature

Silencing circSLAMF6 represses cell glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in gastric cancer under hypoxia.

Project description:Gastric cancer (GC) is a malignant tumor of the digestive tract. Hypoxia plays an important role in the development of cancer, including GC. The present study aimed to investigate the role of circular RNA SLAMF6 (circSLAMF6) in the progression of GC under hypoxia. The expression of circSLAMF6, microRNA-204-5p (miR-204-5p) and myosin heavy chain 9 (MYH9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GC cells were maintained under hypoxia (1% O2) for experiments in vitro. Glucose consumption and lactate production were determined by a Glucose Assay Kit and a Lactate Assay Kit, respectively. Levels of all protein were detected by Western blot. Cell migration and invasion were examined by Transwell assay. The interaction between miR-204-5p and circSLAMF6 or MYH9 was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Murine xenograft model was established to explore the role of circSLAMF6 in vivo. CircSLAMF6 expression was increased in GC cells under hypoxia. Hypoxia promoted glycolysis, migration, and invasion in GC cells, which were reversed by circSLAMF6 knockdown. CircSLAMF6 was validated as a miR-204-5p sponge, and MYH9 was a target of miR-204-5p. Functionally, miR-204-5p inhibitor weakened the inhibition of circSLAMF6 knockdown on GC cell progression under hypoxia. Besides, MYH9 depletion suppressed glycolysis, migration, and invasion in GC cells under hypoxia. Importantly, circSLAMF6 deficiency inhibited tumor growth in vivo by regulating the miR-204-5p/MYH9 axis. CircSLAMF6 was involved in glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in GC cells under hypoxia.

| S-EPMC7313448 | biostudies-literature

Silencing of circTASP1 inhibits proliferation and induces apoptosis of acute myeloid leukaemia cells through modulating miR-515-5p/HMGA2 axis.

Project description:Acute myeloid leukaemia (AML) is a common hematopoietic disease that is harmful to the lives of children and adults. CircRNAs are aberrantly expressed in the haematologic malignancy cells. However, the expression of circTASP1 and its function in AML remain unclear. In this study, we showed that circTASP1 was significantly up-regulated in AML peripheral blood samples and cells. Knockdown of circTASP1 inhibited proliferation and promoted apoptosis of HL60 and THP-1 cells in vitro. Bioinformatics prediction and luciferase reporter assay proved that circTASP1 sponged miR-515-5p and negatively regulated miR-515-5p expression in HL60 and THP-1 cells. High mobility group A2 (HMGA2) was proved to be a downstream target of miR-515-5p. The rescue experiments confirmed that knockdown of circTASP1 inhibited proliferation and induced apoptosis by modulating miR-515-5p/HMGA2 pathway. Moreover, the in vivo experiment indicated that knockdown of circTASP1 suppressed tumour growth. In conclusion, circTASP1 acts as a sponge for miR-515-5p to regulate HMGA2, thereby promoting proliferation and inhibiting apoptosis during AML progression. Thus, circTASP1 has the potential to be explored as a therapeutic target for AML treatment.

| S-EPMC8335685 | biostudies-literature

Hypoxia-associated circDENND2A promotes glioma aggressiveness by sponging miR-625-5p.

Project description:BackgroundAs a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. However, the functions of different circRNAs in gliomas remain elusive.MethodsThe levels of circRNAs, miRNAs, and mRNAs were quantified by qPCR. The interaction between circDENND2A and miR-625-5p was determined by luciferase reporter and pull-down assays. The migratory and invasive capabilities of glioma cells were examined by wound healing and Transwell assays. Immunohistochemistry was performed to analyze the HIF1α level in glioma tissues.ResultsWe predicted circDENND2A (has_circ_0002142) to be a hypoxia-responsive circRNA in glioma via a bioinformatic analysis. We found that hypoxia induced the expression of circDENND2A, which promoted migration and invasion of glioma cells. To understand the behaviors of circDENND2A in glioma, we studied the putative miRNAs targeted by circDENND2A and identified circDENND2A as an efficient sponge of miR-625-5p in glioma cells. Phenotype experiments verified that circDENND2A was required for the hypoxia-induced migration and invasion of glioma cells and that this occurred by sponging of miR-625-5p. Notably, glioma tissues overexpressing HIF1α exhibited a high expression of circDENND2A as well as a low expression of miR-625-5p. circDENND2A was negatively correlated with miR-625-5p.ConclusioncircDENND2A is required for the hypoxia-induced malignancy of glioma cells and functions by sponging miR-625-5p.

| S-EPMC6446274 | biostudies-literature

Long Non-Coding RNA AGAP2-AS1/miR-628-5p/PTN Axis Modulates Proliferation, Migration, Invasion, and Apoptosis of Glioma Cells.

Project description:Purpose:Long non-coding RNAs (lncRNAs) have been reported to be involved in a variety of cancers, including glioma. However, the exact role and underlying mechanism of lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1) in glioma have not yet been fully elucidated. Methods:The expression levels of AGAP2-AS1, microRNA-628-5p (miR-628-5p) and pleiotrophin (PTN) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. Western blot assay was used to detect the protein level of PTN. The interaction between miR-628-5p and AGAP2-AS1 or PTN was predicted by bioinformatics software and confirmed by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Murine xenograft model was established to confirm the role of AGAP2-AS1 in glioma progression in vivo. Results:AGAP2-AS1 expression was upregulated in glioma tissues and cells. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion, but facilitated apoptosis in glioma cells. Moreover, AGAP2-AS1 could directly bind to miR-628-5p and its overexpression reversed the anti-tumor effect of miR-628-5p restoration on the progression of glioma cells. In addition, miR-628-5p directly targeted PTN and its inhibition abolished the inhibitory effect of PTN knockdown on the progression of glioma cells. Furthermore, AGAP2-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-628-5p to modulate PTN expression. Besides, AGAP2-AS1 depletion reduced tumor growth by upregulating miR-628-5p and downregulating PTN. Conclusion:AGAP2-AS1 knockdown suppressed cell proliferation, migration and invasion but promoted cell apoptosis in glioma cells by regulating miR-628-5p/PTN axis, providing novel avenues for treatment of glioma.

| S-EPMC7398883 | biostudies-literature

Hypoxia-responsive miRNA-21-5p inhibits Runx2 suppression by targeting SMAD7 in MC3T3-E1 cells.

Project description:Sustained hypoxia inhibits osteogenesis and osteoblast differentiation by downregulating the expression of runt-related transcription factor 2 (Runx2). MicroRNAs (miRNAs) have been shown to regulate osteogenesis and osteoblast differentiation. In the present study, we profiled miRNAs, with microRNA array and quantitative real-time polymerase chain reaction (RT-PCR) methods, in mouse osteoblast (MC3T3-E1) cells under hypoxia. Then, we investigated regulation by miRNA-21-5p on the expression of Runx2 and other osteoblast differentiation-associated markers via gain-of-function and loss-of-function strategies. We found that expression of miRNA-21-5p, miRNA-210-5p, and other eight miRNAs was upregulated significantly in hypoxia-treated MC3T3-E1 cells. miRNA-21-5p overexpression downregulated the expression of the mRNA and protein of suppressor of mothers against decapentaplegic (SMAD7) markedly, the 3'-untranslated region (3'-UTR) of which was highly homologous with the miRNA-21-5p sequence. miRNA-21-5p overexpression upregulated the protein expression of Runx2 in hypoxia-treated MC3T3-E1 cells, although mRNA expression of Runx2 and other osteoblast differentiation-associated molecules (eg, osteocalcin, procollagen type 1 amino-terminal propeptide, P1NP) were not regulated by it; such upregulation was SMAD7-dependent. In conclusion, hypoxia-responsive miRNA-21-5p promoted Runx2 expression (at least in part) by targeting the 3'-UTR and downregulating SMAD7 expression. Our study suggests a protective role of miRNA-21-5p in promoting osteoblast differentiation under hypoxia.

| S-EPMC6766843 | biostudies-other

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

Project description:Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were significantly lower in GBC than adjacent non-cancer tissues, and which were also associated with patient prognosis. While miR-218-5p overexpression abrogated gemcitabine resistance of GBC cells, silencing of which exhibited the opposite effects. Via six microRNA targets prediction algorithms, we found that PRKCE is a potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the luciferase activity of reporter constructs containing 3'-UTR of PRKCE and also reduced PRKCE expression. Further studies revealed that miR-218-5p promotes sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of MDR1/P-gp. Taken together, our results imply that an intimate correlation between miR-218-5p and PRKCE/MDR1 axis abnormal expression is a key determinant of gemcitabine tolerance, and suggest a novel miR-218-5p-based clinical intervention target for GBC patients.

| S-EPMC5520703 | 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