Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Circular RNA hsa_circ_0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression.

ABSTRACT:

Background

FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa_circ_0068871 is a circRNA generated from several exons of FGFR3. However, the potential functional role of hsa_circ_0068871 in BCa remains largely unknown. Here we aim to evaluate the role of hsa_circ_0068871 in BCa.

Methods

We selected miR-181a-5p as the potential target miRNA of hsa_circ_0068871. The expression levels of hsa_circ_0068871 and miR-181a-5p were examined in BCa tissues and paired adjacent normal tissues by quantitative real-time PCR. To characterize the function of hsa_circ_0068871, BCa cell lines were stably infected with lentivirus targeting hsa_circ_0068871, followed by examinations of cell proliferation, migration and apoptosis. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0068871 in BCa. Biotinylated RNA probe pull-down assay, fluorescence in situ hybridization and luciferase reporter assay were conducted to confirm the relationship between hsa_circ_0068871, miR-181a-5p and FGFR3.

Results

Hsa_circ_0068871 is over-expressed in BCa tissues and cell lines, whereas miR-181a-5p expression is repressed. Depletion of has_circ_0068871 or upregulation of miR-181a-5p inhibited the proliferation and migration of BCa cells in vitro and in vivo. Mechanistically, hsa_circ_0068871 upregulated FGFR3 expression and activated STAT3 by targeting miR-181a-5p to promote BCa progression.

Conclusions

Hsa_circ_0068871 regulates the miR-181a-5p/FGFR3 axis and activates STAT3 to promote BCa progression, and it may serve as a potential biomarker.

SUBMITTER: Mao W

PROVIDER: S-EPMC6472097 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Circular RNA FOXO3 Suppresses Bladder Cancer Progression and Metastasis by Regulating MiR-9-5p/TGFBR2.

Project description:Background:Increasing evidence indicates that the dysregulation of circular RNAs (circRNAs) plays important roles in tumor progressions. Methods:In this study, we first analyzed circ-FOXO3 level in bladder cancers (BCs), and then BC cell lines were transfected with circ-FOXO3 expression vector, and cell proliferation, migration, and invasion abilities were analyzed. We also used bioinformatics tools to predict potential-binding miRNAs for circ-FOXO3, and luciferase reporter assay was used for the verification of binding miRNAs. For the further study, we analyzed potential downstream-binding mRNA for miRNA, and cell proliferation, migration and invasion abilities of it were also studied. Results:We found that circ-FOXO3 was significantly down-regulated in bladder cancer (BC) tissues compared to normal bladder tissues. We also found that circ-FOXO3 overexpression inhibited cell proliferation, migration and invasion in BC cell lines. Moreover, we demonstrated that TGFBR2 was regulated by circ-FOXO3 through sponging miR-9-5p, the knockdown of TGFBR2 or the overexpression of miR-9-5p all related to the increased BC cell proliferation, migration, and invasion. Discussion:In summary, our data showed that circ-FOXO3 was significantly down-regulated in bladder cancers. circ-FOXO3 overexpression inhibits BC cell progression and metastasis. Furthermore, circ-FOXO3 regulates TGFBR2 expression through sponging miR-9-5p in BC cell lines.

| S-EPMC7323812 | biostudies-literature

Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression.

Project description:Growing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B-miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

| S-EPMC8257720 | biostudies-literature

Circular RNA TAF4B Promotes Bladder Cancer Progression by Sponging miR-1298-5p and Regulating TGFA Expression.

Project description:BackgroundBladder cancer (Bca) is the most common malignant tumor of the urinary system. Circular RNAs (circRNAs) have been recognized as key regulators in tumorigenesis. However, the molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown.MethodsWe detected the expression level of circular RNA TAF4B (circTAF4B) by qRT-PCR assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Wound healing and Transwell assays were performed to measure cell migration and invasion capability. Moreover, we performed qRT-PCR and western blotting assays to determine the expression levels of epithelial-mesenchymal transition (EMT) markers. A nuclear/cytoplasmic fractionation assay was used to measure the subcellular location of circTAF4B. RNA pull-down and dual-luciferase reporter assays were used to detect the target microRNA of circTAF4B. A mouse xenograft model was produced to analyze the effect of circTAF4B on the tumorigenesis of BCa.ResultsIn this study, we identified a novel circular RNA, circTAF4B, that is significantly upregulated in BCa and correlated with poor prognosis. Downregulated circTAF4B abolished the growth, metastasis and EMT process in BCa cells. Mechanistically, we found that circTAF4B facilitated the expression of transforming growth factor A (TGFA) by sponging miR-1298-5p. Finally, circTAF4B enhanced the proliferation and EMT process of BCa cells in vivo.ConclusionIn summary, our study demonstrated that circTAF4B played a carcinogenic role in the growth, metastasis, and EMT process of BCa by regulating the miR-1298-5p/TGFA axis. Thus, circTAF4B may become a diagnostic and therapeutic target for BCa.

| S-EPMC8312550 | biostudies-literature

Circular RNA circKIF4A Sponges miR-375/1231 to Promote Bladder Cancer Progression by Upregulating NOTCH2 Expression.

Project description:Circular RNAs (circRNAs) have been found to be important mediators of many biological processes in the growth and metastasis of various cancers. However, the potential roles of most circRNAs in the progression of bladder cancer remain unclear. In this research, we investigate the role of circKIF4A (hsa_circ_0007255) in the development and progression of bladder cancer. Detected by qRT-PCR analysis, circKIF4A was significantly upregulated in bladder cancer tissues and cell lines. We conducted CCK-8, colony-formation, transwell and mouse xenograft assays to explore the function of circKIF4A in bladder cancer. Functionally, knockdown of circKIF4A inhibited the proliferation and colony-formation ability of bladder cancer cells. Migration and metastatic ability were dramatically decreased after transfection with small interfering RNA targeting circKIF4A in both in vitro and in vivo assays. Mechanically, luciferase reporter assays and RNA immunoprecipitation assays were carried out to elucidate the underlying molecular mechanism of circKIF4A. The results revealed that circKIF4A sponges miR-375/1231 to promote bladder cancer progression by upregulating NOTCH2. Generally, our research unveils the essential role of circKIF4A-miR-375/1231-NOTCH2 axis in bladder cancer progression possibly via the competing endogenous RNA mechanism.

| S-EPMC7225260 | biostudies-literature

Tumor-derived exosomal miR-181a-5p activates hepatic stellate cells to promote liver metastasis of colorectal cancer

Project description:A previous study suggested that the expression of miR181a-5p was higher in CRC tissues, but whether CRC cell-derived exosomes regulate the activation of HSCs through secreting miR181a-5p and promoting CRLM warrants further investigation. We compared the miRNA expression profiles between exosomes from highly metastatic CRC cells (RKO and SW620) and those from weakly-metastatic CRC cells (HT29 and SW480).

2021-12-05 | GSE141997 | GEO

Circular RNA circRNA_103809 Accelerates Bladder Cancer Progression and Enhances Chemo-Resistance by Activation of miR-516a-5p/FBXL18 Axis.

Project description:Background:Numerous researches have suggested that circular RNAs (circRNAs) play critical functions in bladder cancer (BC) progression. This study aims to investigate the potential roles of circRNA_103809 in regulating BC development. Methods:qRT-PCR was used to analyze gene expression. CCK8 and colony formation were used to analyze cell proliferation. Transwell was utilized to examine cell migration and invasion. Gemcitabine was used to analyze the effect of circRNA_103809 on the chemo-resistance of BC cells. Luciferase reporter assay was performed to detect the RNA interactions. Results:circRNA_103809 was highly expressed in BC tissues and cell lines. CircRNA_103809 high expression was associated with a poor progression in BC patients. CircRNA_103809 knockdown impaired the growth and metastasis of BC cells. Furthermore, circRNA_103809 silencing increased the sensitivity of BC cells to Gemcitabine treatment. CircRNA_103809 was the sponge for miR-516a-5p and promoted FBXL18 expression via restraining miR-516a-5p activity. Conclusion:circRNA_103809 promotes proliferation, migration, invasion and chemo-resistance of BC cells through regulating miR-516a-5p/FBXL18 axis.

| S-EPMC7457878 | biostudies-literature

Bladder cancer cell‑secreted exosomal miR‑21 activates the PI3K/AKT pathway in macrophages to promote cancer progression.

Project description:Tumour‑associated macrophages (TAMs) compose a major component of the tumour microenvironment and form in this microenvironment prior to cancer metastasis. However, the detailed mechanisms of TAM remodelling in the context of bladder cancer have not been clearly defined. The present study collected exosomes from the conditioned medium of human bladder T24 cancer cells. The effects of macrophages treated with exosomes derived from T24 cells on bladder cancer cell migration and invasion were analysed by Transwell assays. The expression levels of endogenous and exosomal microRNA‑21 (miR‑21) were examined by reverse transcription‑quantitative PCR, while the expression level of the target protein was analysed by western blot analysis. Luciferase reporter plasmids and mutants were used to confirm direct targeting. The effects of miR‑21 on bladder cancer cell migration and invasion were analysed by Transwell and Matrigel assays following miR‑21 transfection. It was identified that exosomes derived from bladder cancer cells polarized THP‑1 cell‑derived macrophages into the M2 phenotype, and TAM‑mediated pro‑migratory and pro‑invasive activity was determined. Moreover, it was found that miR‑21 was highly expressed in exosomes derived from bladder cancer cells as well as in macrophages treated with exosomes. In addition, macrophages transfected with miR‑21 exhibited M2 polarization and promoted T24 cell migratory and invasive ability. Mechanistically, exosomal miR‑21 derived from bladder cancer cells inhibited phosphatase and tensin homolog activation of the PI3K/AKT signalling pathway in macrophages and enhanced STAT3 expression to promote M2 phenotypic polarization. The present results suggest that exosomal miR‑21 can promote cancer progression by polarizing TAMs.

| S-EPMC6910194 | biostudies-literature

Long non-coding RNA CCAT1 promotes colorectal cancer progression by regulating miR-181a-5p expression.

Project description:The vital roles of long noncoding RNAs (lncRNAs) have been implicated in growing number of studies in tumor development. LncRNA CCAT1 has been recognized as associated with tumor development, yet its relation with colorectal cancer (CRC) remains elusive. Our study aimed at elucidating the function and mechanisms of long non-coding RNA CCAT1 in CRC. From a lncRNA profile dataset of 38 pairs of matched tumor-control colon tissues from colorectal patients housed in The Cancer Genome Atlas (TCGA), we detected 10 upregulated and 10 down-regulated lncRNAs in CRC. Fifty cases of CRC patients were enrolled to analyze the correlation between the expression of CCAT1 and clinical pathology. The inverse correlation of expression and target relationship between CCAT1 and miR-181a-5p were verified using qRT-PCR and dual-luciferase reporter gene assay. Cell viability, colony formation ability, aggression and apoptosis were determined by MTT assay, colony formation assay, Transwell and wound healing assays and flow cytometry analysis. Furthermore, Xenograft model was used to show that knockdown of CCAT1 inhibits tumor growth in vivo. The expression of lncRNA CCAT1 was significantly upregulated in CRC tissues. The CCAT1 expression was positively associated with cancer stage (American Joint Committee on Cancer stage, P<0.05). CCAT1 promoted cell proliferation, growth and mobility by targeting miR-181a-5p and the silence of CCAT1 increased the cell apoptosis. Same effect was observed in an in vivo xenograft model, which the tumor size and pro-tumor proteins were significantly diminished by knocking down of CCAT1.

| S-EPMC7244037 | biostudies-literature

MiR-181a-5p promotes osteogenesis by targeting BMP3.

Project description:High-throughput microRNA (miRNA) sequencing of osteoporosis was analyzed from the Gene Expression Omnibus (GEO) database to investigate specific microRNAs that control osteogenesis. MiR-181a-5p was differentially expressed among healthy subjects and those with osteoporosis. Inhibitors and mimics were transfected into cells to modulate miR-181a-5p levels to examine the role in MC3T3-E1 functions. Alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining were used for morphological detection, and proteins of ALP and Runt-related transcription factor 2 (RUNX2), as osteogenesis markers, were detected. During the osteogenic differentiation of MC3T3-E1, the transcription level of miR-181a-5p was significantly increased. The inhibition of miR-181a-5p suppressed MC3T3-E1 osteogenic differentiation, whereas its overexpression functioned oppositely. Consistently, the miR-181a-5p antagomir aggravated osteoporosis in old mice. Additionally, we predicted potential target genes via TargetScan and miRDB and identified bone morphogenetic protein 3 (BMP3) as the target gene. Moreover, the reduced expression of miR-181a-5p was validated in our hospitalized osteoporotic patients. These findings have substantial implications for the strategies targeting miR-181a-5p to prevent osteoporosis and potential related fractures.

| S-EPMC9970307 | biostudies-literature

Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis.

Project description:BACKGROUND:Circular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored. METHODS:Levels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesis in bladder cancer cells. The relationships of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p were predicted using bioinformatic tools and verified by RNA-FISH, RIP and luciferase assays. The effects of circ_0008532 on the Notch signaling pathway were determined by GSEA analysis and western blotting assay. RESULTS:We found that circ_0008532 is upregulated in BC cell lines and tissues. Moreover, overexpression of circ_0008532 promotes, and silencing of circ_0008532 inhibits the capacity for invasive in BC cells. In addition, circ_0008532 can directly interact with miR-155-5p and miR-330-5p as an miRNA sponge which mediates the expression of the miR-155-5p/miR-330-5p target gene MTGR1 and downstream Notch signaling. CONCLUSIONS:Circ_0008532 may act as an oncogene in BC through a novel circ_0008532/miR-155-5p, miR-330-5p /MTGR1/Notch pathway axis, which in turn may provide potential biomarkers and a therapeutic target for the management of bladder cancer.

| S-EPMC7251916 | 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