Browse
Submit Data
Databases
API
Help

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long non‑coding RNA PCED1B‑AS1 promotes pancreatic ductal adenocarcinoma progression by regulating the miR‑411‑3p/HIF‑1α axis.

ABSTRACT: An increasing number of studies have shown that long non‑coding RNAs (lncRNAs) are crucially involved in tumorigenesis. However, the biological functions, underlying mechanisms and clinical value of lncRNA PC‑esterase domain containing 1B‑antisense RNA 1 (PCED1B‑AS1) in pancreatic ductal adenocarcinoma (PDAC) have not been determined, to the best of our knowledge. In the present study, the expression of PCED1B‑AS1, microRNA (miR)‑411‑3p and hypoxia inducible factor (HIF)‑1α mRNA in 47 cases of PDAC tissues were detected using reverse transcription‑quantitative (RT‑q)PCR. Moreover, the effects of PCED1B‑AS1 on the biological behaviors of PDAC cells were assessed using Cell Counting Kit‑8, EdU staining and Transwell assays. Bioinformatics analysis, RT‑qPCR, western blotting, dual luciferase reporter gene and RNA immunoprecipitation assays were performed to determine the regulatory relationships between PCED1B‑AS1, miR‑411‑3p and HIF‑1α. We demonstrated that PCED1B‑AS1 was significantly upregulated in PDAC tumor tissues, and its expression was associated with advanced Tumor‑Node‑Metastasis stage and lymph node metastasis. PCED1B‑AS1 knockdown inhibited PDAC cell proliferation, invasion as well as epithelial‑mesenchymal transition (EMT) in vitro. Mechanistically, PCED1B‑AS1 was shown to target miR‑411‑3p, resulting in the upregulation of HIF‑1α. In conclusion, PCED1B‑AS1 expression was upregulated in PDAC tissues and cells, and it participated in promoting the proliferation, invasion and EMT of cancer cells by modulating the miR‑411‑3p/HIF‑1α axis.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8144929 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway.

Project description:Hepatocellular carcinoma (HCC) is the most common type of liver cancer with poor clinical outcomes. Long non-coding RNAs (lncRNAs) are extensively involved in the tumorigenesis and progression of HCC. However, more investigations should be carried out on novel lncRNAs and their effects on HCC. Here we identified a novel lncRNA KDM4A-AS1, which was aberrantly overexpressed in HCC tissues, associated with unfavorable clinical features and poor prognosis of patients. KDM4A-AS1 promoted HCC cell proliferation, migration, and invasion in vitro and contributed to HCC growth and lung metastasis in vivo. Mechanistically, KDM4A-AS1 was inversely modulated by miR-411-5p at the post-transcriptional level and facilitated Karyopherin α2 (KPNA2) expression by competitively binding miR-411-5p, thereby activating the AKT pathway. KPNA2 silencing, miR-411-5p overexpression, and AKT inhibitor (MK2206) consistently reversed KDM4A-AS1-enhanced proliferation, mobility, and EMT of HCC cells. KDM4A-AS1 was identified as a novel hypoxia-responsive gene and transactivated by hypoxia-inducible factor 1α (HIF-1α) in HCC cells. In turn, KDM4A-AS1 regulated HIF-1α expression through the KPNA2/AKT signaling pathway. Hence, this study revealed a novel hypoxia-responsive lncRNA, KDM4A-AS1, which contributed to HCC growth and metastasis via the KDM4A-AS1/KPNA2/HIF-1α signaling loop. Our findings provide a promising prognostic and therapeutic target for HCC.

| S-EPMC8668937 | biostudies-literature

A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1α in pancreatic ductal adenocarcinoma.

Project description:BackgroundInvasion and metastasis are the distinct biologic characteristics of cancer, resulting in an exceptionally low 5-year survival rate in pancreatic ductal adenocarcinoma (PDAC). Understanding in detail the mechanisms underlying PDAC metastasis is critical for prevention and effective interventions. Long non-coding RNAs (lncRNAs) have been documented as having a critical role in cancer development and progression.MethodsWe examined the expression levels of lncRNA ENST00000480739 and osteosarcoma amplified-9 (OS-9) mRNA in a cohort of 35 PDAC patients. Cell proliferation, invasion and migration were examined with and without ENST00000480739 overexpression in PDAC cells.ResultsWe determined that the ENST00000480739 expression level was remarkably decreased in tumorous tissues compared with their corresponding non-tumorous tissues. The expression of ENST00000480739 was negatively associated with tumour node metastasis stage and lymph node metastasis. In addition, ENST0000048073 was an independent prognostic factor of survival time in PDAC patients following surgery. Besides, enforced expression of ENST00000480739 suppressed PDAC cells' invasion in vitro. Overexpression of ENST00000480739 significantly increased both mRNA and protein levels of OS-9, and the luciferase assays confirmed that ENST00000480739 positively regulates OS-9 by activating the transcription level of the OS-9 promoter. We further found that ENST00000480739 may target hypoxia-inducible factor-1α (HIF-1α) expression by upregulating OS-9.ConclusionsThese findings suggest that the frequently downregulated ENST00000480739 in PDAC contributes to tumour metastasis and progression by regulating HIF-1α. Long non-coding RNA ENST00000480739 may provide not only a therapeutic potential to suppress metastasis but it may also be a novel biomarker for risk prognostication and personal therapy screening of PDAC patients.

| S-EPMC4260035 | biostudies-literature

LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1α/ glycolysis axis in lung adenocarcinoma.

Project description:Background: Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in lung adenocarcinoma have not been fully elucidated. Methods: We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1α expression, degradation, and its binding to VHL. Moreover, an in vivo subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD. Results: Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells in vivo and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines in vitro and in vivo, and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1α degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1α and glycolysis-related genes in vivo. Conclusion: Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1α/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients.

| S-EPMC8741836 | biostudies-literature

NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma.

Project description:It is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF-1-related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer-associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT-AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT-AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR was used to evaluate the expression of NNT-AS1, miR-889-3p, and HIF-1. The role of CAFs-derived exosomal NNT-AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT-AS1, miR-889-3p, and HIF-1. After PDAC cells co-culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF-derived exosomal lncRNA NNT-AS1 acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted by miR-889-3p and was controlled by NNT-AS1. This study explores the mechanism by which NNT-AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR-889-3p/HIF-1α, which also helps discover new clinical treatment targets for PDAC.

| S-EPMC10960871 | biostudies-literature

SCF, regulated by HIF-1α, promotes pancreatic ductal adenocarcinoma cell progression.

Project description:Stem cell factor (SCF) and hypoxia-inducible factor-1α (HIF-1α) both have important functions in pancreatic ductal adenocarcinoma (PDAC). This study aims to analyze the expression and clinicopathological significance of SCF and HIF-1α in PDAC specimens and explore the molecular mechanism at PDAC cells in vitro and in vivo. We showed that the expression of SCF was significantly correlated with HIF-1α expression via Western blot, PCR, chromatin immunoprecipitation (ChIP) assay, and luciferase assay analysis. The SCF level was also correlated with lymph node metastasis and the pathological tumor node metastasis (pTNM) stage in PDAC samples. The SCF higher-expression group had significantly lower survival rates than the SCF lower-expression group (p<0.05). Hypoxia up-regulated the expression of SCF through the hypoxia-inducible factor (HIF)-1α in PDAC cells at the protein and RNA levels. When HIF-1α was knocked down by RNA interference, the SCF level decreased significantly. Additionally, ChIP and luciferase results demonstrated that HIF-1α can directly bind to the hypoxia response element (HRE) region of the SCF promoter and activate the SCF transcription under hypoxia. The results of colony formation, cell scratch, and transwell migration assay showed that SCF promoted the proliferation and invasion of PANC-1 cells under hypoxia. Furthermore, the down-regulated ability of cell proliferation and invasion following HIF-1α knockdown was rescued by adding exogenous SCF under hypoxia in vitro. Finally, when the HIF-1α expression was inhibited by digoxin, the tumor volume and the SCF level decreased, thereby proving the relationship between HIF-1α and SCF in vivo. In conclusion, SCF is an important factor for the growth of PDAC. In our experiments, we proved that SCF, a downstream gene of HIF-1α, can promote the development of PDAC under hypoxia. Thus, SCF might be a potential therapeutic target for PDAC.

| S-EPMC4370420 | biostudies-literature

Long non-coding RNA ZEB1-AS1 promotes colon adenocarcinoma malignant progression via miR-455-3p/PAK2 axis.

Project description:ObjectiveThe long non-coding RNA zinc finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) acts as an oncogenic regulator in many human tumours. In the present study, we identify the role and potential molecular biological mechanisms of ZEB1-AS1 in colon adenocarcinoma (COAD).MethodsQRT-PCR was used to detect the expression of ZEB1-AS1, miR-455-3p and p21-activated kinases 2 (PAK2) in COAD tissues. CCK8 assay, EdU assay, transwell assay and scratch wound assay were used to explore the biological function of ZEB1-AS1 in COAD cells. Bioinformatics, luciferase reporter assays and an RNA pull-down assay were used to demonstrate the mechanism of ZEB1-AS1. We further explore the role of ZEB1-AS1 in vivo though xenograft tumour assay.ResultsWe found that ZEB1-AS1 expression was significantly up-regulated in COAD tissues, and high ZEB1-AS1 level was correlated with the poor prognosis of COAD patients. MiR-455-3p plays an anti-cancer role in COAD by targeting PAK2. We confirmed that ZEB1-AS1 promotes PAK2 expression by sponging miR-455-3p, thus facilitating COAD cell growth and metastasis.ConclusionsTo sum up, this result illustrates the novel molecular mechanism of ZEB1-AS1 in COAD and provides a new target for the diagnosis and treatment of COAD patients.

| S-EPMC6985675 | biostudies-literature

LncRNA TTN-AS1 promotes the progression of oral squamous cell carcinoma via miR-411-3p/NFAT5 axis.

Project description:Background:Oral squamous cell carcinoma (OSCC) is a common kind of squamous cell carcinoma of the head and neck, which is a threat to public health. Long noncoding RNAs (lncRNAs) are associated with the development of various diseases, including cancers. LncRNA titin antisense RNA 1 (TTN-AS1) is known as a crucial regulatory factor in several cancers. Nevertheless, the specific functions of TTN-AS1 in OSCC remains obscure. Methods:The expression of TTN-AS1 in OSCC samples or cells was analyzed through qRT-PCR. Colony formation assay, EdU assay, flow cytometry assay, TUNEL assay and wound healing assay were conducted to estimate the functions of TTN-AS1 in OSCC cells. RIP and luciferase reporter assays were utilized to detect the interaction between TTN-AS1 and miR-411-3p as well as between miR-411-3p and NFAT5. Results:TTN-AS1 expression was stronger in OSCC cells. Knockdown of TTN-AS1 effectively restrained cell proliferation and migration but had inductive role in apoptosis. Moreover, TTN-AS1 could function as the miR-411-3p sponge in OSCC and miR-411-3p exerted the inhibitory functions on OSCC cell growth. In addition, NFAT5 was proven as the target of miR-411-3p. Rescue assay indicated that overexpressing NFAT5 could reverse the inhibitory function of TTN-AS1 depletion on cell growth. Conclusion:lncRNA TTN-AS1 contributed to the progression of OSCC via miR-411-3p/NFAT5 axis.

| S-EPMC7453543 | biostudies-literature

Long Non-Coding RNA SLC25A21-AS1 Promotes Multidrug Resistance in Nasopharyngeal Carcinoma by Regulating miR-324-3p/IL-6 Axis.

Project description:BackgroundNasopharyngeal carcinoma (NPC), one of the most common types of head and neck tumor, occurred in the epithelial lining of the nasopharynx and is mainly prevalent in Southeast Asia and Southern China. However, the molecular mechanisms of NPC multidrug resistance still remained largely unclear.MethodsThe qRT-PCR assay was performed to examine SLC25A21-AS1, miR-324-3p and IL-6 expression in NPC tissues and cell. The CCK8 assay and colony formation assay were used to detect cell growth. In addition, CCK8 assay was performed to detect IC50 values of different drugs in NPC cell.ResultsIn this study, we found that SLC25A21-AS1 expression was increased in NPC tissues and cell line, and knockdown of SLC25A21-AS1 inhibited cell growth and MDR in NPC cell. Moreover, SLC25A21-AS1 acted as a ceRNA for miR-324-3p and facilitates NPC cell growth and MDR by regulating the miR-324-3p/IL-6 axis.ConclusionOur findings demonstrated the role of SLC25A21-AS1/miR-324-3p/IL-6 axis in cell growth and MDR in NPC, which might be a potential prognostic and diagnostic marker in NPC patients and provide new insight into the molecular mechanism of MDR in NPC chemotherapy.

| S-EPMC7264158 | biostudies-literature

Long non-coding RNA VCAN-AS1 promotes the malignant behaviors of breast cancer by regulating the miR-106a-5p-mediated STAT3/HIF-1α pathway.

Project description:An accumulating number of studies have found that long noncoding RNAs (lncRNAs) participate in breast cancer (BC) development. LncRNA VCAN-AS1, a novel lncRNA, has been confirmed to regulate the progression of gastric cancer, while its role in BC is elusive. Here, our results illustrate that VCAN-AS1 is overexpressed in BC tissues and cells, while miR-106a-5p was downregulated and negatively correlated with VCAN-AS1. In addition, high VCAN-AS1 expression and low miR-106a-5p expression were closely correlated with poor overall survival in BC patients. Functional experiments confirmed that VCAN-AS1 overexpression notably accelerated BC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and enhanced tumor cell growth while also suppressing cell apoptosis. However, overexpression of miR-106a-5p had the opposite effects. In addition, rescue experiments confirmed that overexpression of VCAN-AS1 inhibited the tumor-suppressive effects mediated by miR-106a-5p. Mechanistically, through bioinformatics analysis, we found that VCAN-AS1 functions as a competitive endogenous RNA (ceRNA) of miR-106a-5p, which targets the 3' untranslated region (UTR) of signal transducer and activator of transcription 3 (STAT3). Further experiments indicated that miR-106a-5p downregulated the STAT3/hypoxia-inducible factor-1alpha (HIF-1α) pathway, while activating the STAT3 pathway reversed miR-106a-5p-mediated antitumor effects. Collectively, our data suggest that VCAN-AS1 is upregulated in breast cancer and promotes its progression by regulating the miR-106a-5p-mediated STAT3/HIF-1α pathway. This study provides a new target for BC therapy.

| S-EPMC8806652 | biostudies-literature

Long non-coding RNA KTN1-AS1 promotes progression in pancreatic cancer through regulating microRNA-23b-3p/high-mobility group box 2 axis.

Project description:To explore the inhibitory effect of long non-coding RNA (LncRNA) antisense of KTN1 (KTN1-AS1) on the growth of pancreatic cancer (PC) cells by regulating the microRNA-23b-3p (miR-23b-3p)/high-mobility group box 2 (HMGB2) axis. The expression of KTN1-AS1 in tissues and cells was detected by qRT-PCR, and the relationship between KTN1-AS1 and clinicopathological data of patients with PC was analyzed. In addition, stable and transient overexpression and inhibition vectors were established and transfected into PC cells PANC-1, BxPC-3. CCK-8, transwell, and flow cytometry were responsible for the detection of proliferation, invasion, and apoptosis of transfected cells, respectively. The correlation of miR-23b-3p between KTN1-AS1 and HMGB2 was determined by dual luciferase reports, and the relationship between KTN1-AS1 and miR-23b-3p was further verified by RNA immunoprecipitation (RIP). The highly expressed KTN1-AS1 in PC patients was indicative of its high diagnostic value in this disease. Besides, it was found that KTN1-AS1 was linked with the pathological stage, differentiation degree and lymph node metastasis (LNM) of PC patients. Underexpressed KTN1-AS1 led to decreased proliferation and invasion ability of cells and increased apoptosis rate, while the effect of further overexpression of KTN1-AS1 on cells was the opposite. Dual luciferase reporter (DLR) assay confirmed that KTN1-AS1 could target miR-23b-3p, while miR-23b-3p could target HMGB2. Functional analysis showed that the overexpression of miR-23b-3p inhibited the expression of HMGB2 in PC cells and affected cell proliferation, invasion and apoptosis. Co-transfection of Sh-KTN1-AS1 and miR-23b-3p-mimics exhibited that up-regulation of KTN1-AS1 expression could reverse the effect of miR-23b-3p-mimics on PC cells.

| S-EPMC8436926 | 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