Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Upregulated osteoprotegerin expression promotes lung cancer cell invasion by increasing miR-20a expression.

ABSTRACT: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and a major regulatory factor in osteoclast development. OPG has been previously associated with the malignant behavior of various types of cancer, particularly that of cancer metastasis. However, information on the link between the expression profile of OPG and lung cancer metastasis remained elusive. In the present study, the expression levels of OPG in the serum samples of patients with non-small cell lung cancer (NSCLC) was measured using ELISA. The expression of miRNAs was assessed using reverse transcription-quantitative PCR. A549 or H3122 cell invasion was assessed using Transwell invasion assays. The effect of OPG on the invasiveness of lung cancer cells was evaluated using an experimental mouse lung metastasis model. OPG expression was found to be upregulated in the serum of patients with NSCLC compared with that in healthy individuals. The serum levels of OPG in patients with distant metastasis were observably higher compared with those in patients without metastasis. Functionally, overexpression of OPG in NSCLC cells markedly promoted cell invasion. Mechanistically, increased expression of OPG resulted in upregulation of microRNA (miR)-20a in NSCLC cells. Furthermore, miR-20a promoted NSCLC cell invasion, whilst miR-20a inhibition partially abrogated the effect of OPG on NSCLC cell invasion. Taken together, the present results demonstrated that the OPG/miR-20a axis serve an important role in lung cancer metastasis, which potentially provide an additional novel target for lung cancer treatment.

SUBMITTER: Wan K

PROVIDER: S-EPMC8210324 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

RBAK is upregulated in non-small cell lung cancer and promotes cell migration and invasion.

Project description:Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide, NCSCLC includes lung adenocarcinoma and lung squamous cell carcinoma. Tumor metastasis is the major cause of mortality of patients with NSCLC. However, the mechanisms underlying NSCLC metastasis remain largely elusive. In present study, the authors focused on exploring the roles of RBAK in NSCLC. The present study demonstrated that RB-associated KRAB zinc finger (RBAK) was upregulated in NSCLC compared with non-tumorous tissues by analyzing Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) dataset. High expression of RBAK was associated with poor disease-free survival of patients with NSCLC by analyzing TCGA dataset. Furthermore, an RBAK-mediated protein-protein interaction network was constructed to reveal the potential underlying mechanisms by which RBAK drives NSCLC progression. The authors found that RBAK was involved in regulating a number of transcription factors, including androgen receptor, forkhead box A1, tumor protein 53, and E2F transcription factor 1, 2 and 4, suggesting that RBAK may have a role in regulating gene transcription. GO and KEGG enrichment analyses of the genes co-expressed with RBAK revealed that RBAK is involved in regulating a number of biological functions, including the Wnt signaling pathway, mRNA splicing, protein polyubiquitination, cell-cell adhesion and focal adhesion. Transwell and wound healing assays demonstrated that knockdown of RBAK suppressed NSCLC cell migration and invasion. The present study enhances the current understanding of the important roles of RBAK in NSCLC metastasis and may provide useful information for the development of novel treatment approaches.

| S-EPMC6755425 | biostudies-literature

MiR-20a is upregulated in anaplastic thyroid cancer and targets LIMK1.

Project description:BackgroundThere have been conflicting reports regarding the function of miR-20a in a variety of cancer types and we previously found it to be dysregulated in sporadic versus familial papillary thyroid cancer. In this study, we studied the expression of miR-20a in normal, benign and malignant thyroid samples, and its effect on thyroid cancer cells in vitro and in vivo.Methodology/principal findingsThe expression of miR-20a in normal, benign and malignant thyroid tissue was determined by quantitative RT-PCR. Thyroid cancer cells were transfected with miR-20a and the effect on cellular proliferation, tumor spheroid formation, and invasion was evaluated. Target genes of miR-20 were determined by genome-wide mRNA expression analysis with miR-20a overexpression in thyroid cancer cells and target prediction database. Target genes were validated by quantitative PCR and immunoblotting, and luciferase assays. MiR-20a expression was significantly higher in anaplastic thyroid cancer than in differentiated thyroid cancer, and benign and normal thyroid tissues. MiR-20a significantly inhibited thyroid cancer cell proliferation in vitro (p<0.01) and in vivo (p<0.01), tumor spheroid formation (p<0.05) and invasion (p<0.05) in multiple thyroid cancer cell lines. We found that LIMK1 was a target of miR-20a in thyroid cancer cell lines and direct knockdown of LIMK1 recapitulated the effect of miR-20a in thyroid cancer cells.Conclusions/significanceTo our knowledge, this is the first study to demonstrate that miR-20a plays a role as a tumor suppressor in thyroid cancer cells and targets LIMK1. Our findings suggest the upregulated expression of miR-20a in anaplastic thyroid cancer counteracts thyroid cancer progression and may have therapeutic potential.

| S-EPMC4032243 | biostudies-literature

miR-20a regulates expression of the iron exporter ferroportin in lung cancer.

Project description:Ferroportin (FPN) exports iron from duodenal enterocytes, macrophages, and hepatocytes to maintain systemic iron homeostasis. In addition, FPN is expressed in various cancer cells. Here, we show that in lung cancer, FPN expression is regulated by miR-20a. Within the FPN-3'-untranslated region (3'UTR), we identify and experimentally validate three evolutionarily conserved target sites for the microRNA (miRNA) members of the miR-17 seed family, including miR-20a. Our analysis of RNA sequencing data from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) revealed that FPN messenger RNA (mRNA) levels are significantly decreased in tumor compared to matched healthy tissue, while miR-20a levels are increased. A significant negative correlation of miR-20a and FPN expression was observed. Functional studies further demonstrate that FPN is post-transcriptionally regulated by miR-20a in non-small cell lung cancer (NSCLC) cells and that overexpression or knockdown of miR-20a or FPN affects NSCLC proliferation and colony formation. Taken together, our data suggest that increased expression of miR-20 in lung cancer may decrease iron export, leading to intracellular iron retention, which, in turn, favors cell proliferation.miR-20a controls expression of the iron exporter ferroportin (FPN) by binding to highly conserved target sites in its 3'UTR. Expression of miR-20a is inversely correlated to FPN in lung cancer. Low FPN expression stimulates proliferation and colony formation of non-small cell lung cancer (NSCLC) cells, possibly by increasing iron availability for cancer cell proliferation.

| S-EPMC4803811 | biostudies-other

miR-20a is upregulated in serum from domestic feline with PKD1 mutation.

Project description:Polycystic kidney disease (PKD), also known as autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous condition characterized by cysts in renal parenchyma. It is the most prevalent inherited disease of domestic cats. MicroRNAs (miRNAs or ncRNA) are short, noncoding, single-stranded RNAs that may induce PKD cytogenesis by affecting numerous targets genes as well as by directly regulating PKD gene expression. We compared the relative expression profile of miR-20a, -192, -365, -15b-5p, and -16-5p from plasma and serum samples of nine domestic cats with PKD1 mutation, detected by polymerase chain reaction (PCR), and a control group (n = 10). Blood samples from cats with PKD1 mutation provide similar concentrations of microRNAs either from plasma or serum. Serum miR-20a is upregulated in PKD group with p < 0.005; Roc curve analysis showed an AUC of 90,1% with a cut-off value sensitivity of 77.8% and specificity of 100%. This data provides important information regarding renal miRNA expression in peripheral blood sampling.

| S-EPMC9767353 | biostudies-literature

GDF-11 promotes human trophoblast cell invasion by increasing ID2-mediated MMP2 expression.

Project description:BackgroundGrowth differentiation factor-11 (GDF-11), also known as bone morphogenetic protein-11, belongs to the transforming growth factor-beta superfamily. GDF-11 was first identified as an important regulator during embryonic development. Increasing evidence has demonstrated that GDF-11 regulates the development of various organs and its aberrant expressions are associated with the risk of cardiovascular diseases and cancers. Extravillous trophoblast (EVT) cells invasion is a critical event for placenta development and needs to be finely regulated. However, to date, the biological function of GDF-11 in the human EVT cells remains unknown.MethodsHTR-8/SVneo, a human EVT cell line, and primary cultures of human EVT cells were used to examine the effect of GDF-11 on matrix metalloproteinase 2 (MMP2) expression. Matrigel-coated transwell invasion assay was used to examine cell invasiveness. A series of in vitro experiments were applied to explore the underlying mechanisms that mediate the effect of GDF-11 on MMP2 expression and cell invasion.ResultsTreatment with GDF-11 stimulates MMP2 expression, in the HTR-8/SVneo and primary human EVT cells. Using a pharmacological inhibitor and siRNA-mediated knockdown approaches, our results demonstrated that the stimulatory effect of GDF-11 on MMP2 expression was mediated by the ALK4/5-SMAD2/3 signaling pathways. In addition, the expression of inhibitor of DNA-binding protein 2 (ID2) was upregulated by GDF-11 and that was required for the GDF-11-stimulated MMP2 expression and EVT cell invasion.ConclusionsThese findings discover a new biological function and underlying molecular mechanisms of GDF-11 in the regulation of human EVT cell invasion. Video Abstract.

| S-EPMC9202197 | biostudies-literature

Upregulated circPDK1 Promotes RCC Cell Migration and Invasion by Regulating the miR-377-3P-NOTCH1 Axis in Renal Cell Carcinoma.

Project description:Background:Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are involved in the regulation of multiple biological processes in diverse types of cancers. However, the roles and precise mechanisms of circRNAs in renal cell carcinoma (RCC) occurrence and progression have not been clearly elucidated. Methods:We identified the aberrantly expressed circRNAs in RCC by high-throughput RNA-seq assay and used qRT-PCR to test the expression level of circRNAs in RCC tissues. Loss-of-function experiments were executed to detect the biological roles of circPDK1 in the RCC cells both in vivo and in vitro. RNA Fish, luciferase reporter assays and Western blotting were used to explore the molecular mechanism of circPDK1 function. All data were expressed as the means ± standard error of the mean (SEM). Student's t-test, one-way ANOVA, Cox regression, an LSD-t-test, Pearson's chi-squared test, a Log-rank test, and linear regression analyses were used to evaluate the group differences. P?<?0.05 was considered significant. Results:CircPDK1 was overexpressed in RCC tissues and positively associated with patient tumor metastasis and renal cell invasion. The in vivo functional assays also revealed that circPDK1 drove RCC xenograft metastasis. CircPDK1 was mainly located in the cytoplasm, serving as a sponge of miR-377-3P to regulate RCC invasion and metastasis through NOTCH1 (Notch Homolog 1). Ectopic express of NOTCH1 in RCC cell lines will block the metastasis inhibition effect after circPDK1 knockdown. Conclusion:CircPDK1 is aberrantly expressed in RCC and promotes the metastasis of RCC cells mainly through sponging miR-377-3P and reducing its negative regulation of NOTCH1. Thus, circPDK1 may act as a therapeutic target and biomarker for RCC.

| S-EPMC7648593 | biostudies-literature

Circular RNA ABCB10 promotes non-small cell lung cancer progression by increasing E2F5 expression through sponging miR-584-5p.

Project description:Background/aimsCircABCB10 function as an endogenous miRNA sponge plays an important role in various tumors. This experimental design was based on circABCB10 to explore the pathogenesis of non-small cell lung cancer (NSCLC). Methods: CircRNA microarray was used to examine circRNA expression profiles in lung cancer from 3 NSCLC patients and paired healthy lung tissues. The expression of circABCB10 and miR-584-5p was detected by q-PCR. CCK-8, colony formation, and transwell assays to study the circABCB10 effects on tumor cell growth and cell migration invasiveness. To validate downstream target genes of circABCB10 and miR-584-5p detected by luciferase reporter assays. RT-qPCR and Western blotting were used to study E2F5 expression. The tumor growth was detected by nude mice in vivo. Results: We analyzed the human circRNA expression profile in NSCLC tissues. CircABCB10 was identified as a circRNA that increased in NSCLC tissues. CircABCB10 was noticeably raised in NSCLC, and high circABCB10 expression was related to low survival in NSCLC patients. Silencing of circABCB10 suppressed non-small cell lung cancer cell migration, cell proliferation, and invasion.CircABCB10 can act as a sponge of miR-584-5p to up-regulate E2F5 expression level. E2F5 knockdown or overexpress of miR-584-5p gene reversed the circABCB10 who has carcinogenic effects. There was a negative correlation expression between the circABCB10 and miR-584-5p gene, and There was a positive relationship between the expression of circABCB10 and E2F5 in NSCLC tumors. Conclusion: CircABCB10 promoted the progression of NSCLC by modulating the miR-584-5p/E2F5 axis.AbbreviationNSCLC: non-small cell lung cancer; circ RNA: circular RNA; miRNA: micro RNA.

| S-EPMC7469616 | biostudies-literature

SRCIN1 Regulated by circCCDC66/miR-211 Is Upregulated and Promotes Cell Proliferation in Non-Small-Cell Lung Cancer.

Project description:The incidence and mortality of lung cancer were extremely high. The present study showed that SRCIN1 was an oncogene in non-small-cell lung cancer (NSCLC). Public dataset analysis showed SRCIN1 was significantly overexpressed in NSCLC samples. Also, we found that NSCLC patients with higher SRCIN1 expression had shorter OS time by analyzing TCGA, Kaplan-Meier Plotter, GSE30219, GSE50081, and GSE19188 databases. Overexpression or knockdown of SRCIN1 significantly induced or reduced A549 and H1299 cell proliferation. Furthermore, we found SRCIN1 was directly targeted by miR-211. Overexpression or knockdown of miR-211 suppressed or induced SRCIN1 levels in NSCLC. Moreover, we found that miR-211 affected NSCLC cell proliferation through SRCIN1. Previous studies demonstrated that circRNAs could act as miRNA sponges in cancer cells. In this study, we showed that knockdown of circCCDC66 induced expression of miR-211. Luciferase assay demonstrated that miR-211 suppressed the activity of luciferase reporter-contained circCCDC66 sequences. Moreover, knockdown of circCCDC66 significantly inhibited SRCIN1 levels in both A549 and H1299 cells. These results showed that circCCDC66 acted as a miRNA sponge to affect the miR-211/SRCIN1 axis. Of note, we for the first time revealed that circCCDC66 suppression reduced cell proliferation by about 65% in A549 and by about 40% in H1299 cells. We thought this study could provide novel potential biomarkers for NSCLC.

| S-EPMC7501558 | biostudies-literature

MiR-155 Promotes Uveal Melanoma Cell Proliferation and Invasion by Regulating NDFIP1 Expression.

Project description:MicroRNAs refer to small RNA molecules that destroy the messenger RNA by binding on them inhibiting the production of protein. However, the role of miR-155 in uveal melanoma metastasis remains largely unknown. In this study, we found that miR-155 was upregulated in both uveal melanoma cells and tissues. Transfection of miR-155 mimic into uveal melanoma cells led to an increase in cell growth and invasion; in contrast, inhibition of miR-155 resulted in opposite effects. Also, we identified Nedd4-family interacting protein 1 as a direct target of miR-155, and the expression of Nedd4-family interacting protein 1 was inhibited by miR-155. Furthermore, ectopic expression of Nedd4-family interacting protein 1 restored the effects of miR-155 on cell proliferation and invasion of uveal melanoma cells. In conclusion, miR-155 acts as a tumor promotor in uveal melanoma through increasing cell proliferation and invasion. Thus, miR-155 might serve as a potential therapeutic target in patients with uveal melanoma.

| S-EPMC5762084 | biostudies-other

Hsa_circ_0001666 promotes non-small cell lung cancer migration and invasion through miR-1184/miR-548I/AGO1 axis.

Project description:Accumulating evidence has revealed that the dysregulation of circular RNAs (circRNAs) plays crucial roles in the occurrence and progression of cancers. However, the aberrant expression profile and dysfunction of circRNAs in non-small cell lung cancer (NSCLC) have not been fully explored. Herein, we discovered that a circRNA, hsa_circ_0001666 (circ0001666), was highly expressed in NSCLC tissues and cell lines, and it was positively correlated with NSCLC tumor pathological grade and lymph node metastasis. Moreover, Kaplan-Meier survival analysis implied that NSCLC patients with high circ0001666 expression were negatively correlated with favorable survival. Functionally, circ0001666 could promote migration and invasion of NSCLC cells in vitro and in vivo. Mechanistically, circ0001666 could act as a sponge to miR-1184/miR-548I and upregulate the expression of AGO1, thereby promoting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway in NSCLC cells. Collectively, these findings demonstrated that circ0001666 could serve as an oncogene to promote the migration and invasion of NSCLC via a novel miR-1184/miR-548I/AGO1 axis, which might be a promising therapeutic target for NSCLC treatment.

| S-EPMC8892028 | 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