Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p.

ABSTRACT: To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.

SUBMITTER: Hozaka Y

PROVIDER: S-EPMC8469425 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Identifying genes regulated by miR-490-3p

Project description:To identify the direct target of miR-490-3p, we used whole genome microarray expression profiling to screen for genes potentially regulated by the microRNA.

2014-10-18 | GSE62453 | GEO

MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1.

Project description:BackgroundColorectal cancer (CRC) is one of the most common malignances worldwide. Metastasis is responsible for the rapid recurrence and poor prognosis of CRC. However, the underlying molecular mechanism of CRC metastasis remains largely unclear. In this study we purposed to investigate the expression and biological functions of miR-490-3p in CRC metastasis, as well as to identify its downstream target genes and influenced pathway.MethodsThe expression level of miR-490-3p in CRC cell lines, CRC adjacent normal tissues, non-metastasis and metastasis tissues were assessed by quantitative real-time PCR. Patient survivals were follow-up up to 7 years. Gain-of-function and loss-of-function study on cell migration and invasion abilities were carried out by transfection of miR-490-3p mimics or inhibitors respectively. The molecular targets of miR-490-3p were computationally identified and experimentally verified by dual-luciferase reporter assay and western blot. Functional rescue was also conducted to confirm miR-490-3p inhibits CRC metastasis by targeting TGF-β signaling pathway.ResultsmiR-490-3p expression was persistently downregulated during CRC malignant progression, as well as in CRC cell lines. Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects. TGFβR1 and MMP2/9 were the downstream targets of miR-490-3p in CRC. Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p.ConclusionmiR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway. Taken together, miR-490-3p is acting as a tumor suppressor in CRC.

| S-EPMC4696296 | biostudies-literature

Identifying genes regulated by miR-490-3p

Project description:To identify the direct target of miR-490-3p, we used whole genome microarray expression profiling to screen for genes potentially regulated by the microRNA. AGS cells were transfected with control mimics or miR-490-3p mimics and gene expression was determined 72 hours after transfection.

2014-10-18 | E-GEOD-62453 | biostudies-arrayexpress

MicroRNA signature of small-cell lung cancer after treatment failure: impact on oncogenic targets by miR-30a-3p control.

Project description:Small-cell lung cancer (SCLC) is associated with a high mortality rate and limited treatment efficacy. We created a microRNA (miRNA) expression signature by RNA sequencing using specimens from patients with SCLC who had failed treatment. Forty-nine miRNAs were downregulated in SCLC tissues and were candidate tumor-suppressive miRNAs. In this signature, both guide and passenger strands were downregulated for five miRNAs (miR-30a, miR-34b, miR-34c, miR-223, and miR-4529). Recent studies have revealed that passenger strands of miRNAs are involved in the molecular pathogenesis of human cancer. Although miR-30a-5p (the guide strand) has been shown to be a tumor-suppressive miRNA in various types of cancers, miR-30a-3p (the passenger strand) function is not well characterized in SCLC cells. We investigated the functional significance of miR-30a-3p and oncogenic genes regulated by miR-30a-3p in SCLC cells. Ectopic expression assays showed that miR-30a-3p expression inhibited cell proliferation and induced cell cycle arrest and apoptosis in two SCLC cell lines. Furthermore, in silico database searches and gene expression assays identified 25 genes as putative targets of miR-30a-3p in SCLC cells. Luciferase reporter assays revealed that downstream neighbor of SON (DONSON) was directly regulated by miR-30a-3p in SCLC cells. Knockdown of DONSON induced cell cycle arrest in SCLC cells and DONSON overexpression were detected in SCLC clinical samples. Analyzing the regulatory networks of tumor-suppressive miRNAs may lead to the identification of therapeutic targets in SCLC.

| S-EPMC9892828 | biostudies-literature

CircSLC3A2 functions as an oncogenic factor in hepatocellular carcinoma by sponging miR-490-3p and regulating PPM1F expression.

Project description:BACKGROUND:Non-coding RNAs (ncRNAs) have been reported to participate in tumor progression by regulating gene expression. Previous studies showed that protein phosphatase Mg2+/Mn2+ dependent 1F (PPM1F) acts a dual role in cancer growth and metastasis. But, the underlying mechanisms by which ncRNAs regulate PPM1F expression in hepatocellular carcinoma (HCC) are poorly understood. METHODS:The association between PPM1F or miR-490-3p expression and clinicopathological features and prognosis in patients with HCC was analyzed by TCGA RNA-sequencing data. CircSLC3A2 was identified to bind with miR-490-3p by bioinformatic analysis, and the binding sites between miR-490-3p and PPM1F or circSLC3A2 were confirmed by dual luciferase report and RNA immunoprecipitation (RIP) assays. The localization and clinical significance of miR-490-3p and circSLC3A2 in patients with HCC were investigated by fluorescence in situ hybridization (FISH). MTT, Agar, and Transwell assays were conducted to evaluate the effects of miR-490-3p or circSLC3A2 on cell proliferation and invasive potential. RESULTS:The expression of PPM1F or miR-490-3p was associated with poor survival and tumor recurrence, and acted as an independent prognostic factor in patients with HCC. Re-expression of miR-490-3p inhibited HCC cell proliferation and invasion by targeting PPM1F, but its inhibitor reversed these effects. Moreover, circSLC3A2, predominantly localized in the cytoplasm, exhibited an oncogenic role by sponging miR-490-3p and regulating PPM1F expression, and harbored a positive correlation with poor survival in patients with HCC. CONCLUSION:CircSLC3A2 acts as an oncogenic factor in HCC by sponging miR-490-3p and regulating PPM1F expression.

| S-EPMC6260990 | biostudies-literature

The oncogenic microRNA miR-21 promotes regulated necrosis in mice.

Project description:MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumour necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis and miR-21 enhances cellular necrosis by negatively regulating tumour suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway, and could be a therapeutic target for preventing pathologic necrosis.

| S-EPMC4440243 | biostudies-literature

Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer.

Project description:Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model's performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

| S-EPMC8037203 | biostudies-literature

Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis.

Project description:Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This study aimed to identify the oncogenes closely involved in PDAC molecular pathogenesis under the regulation of miR-30a-3p. Ectopic expression assays showed that miR-30a-3p expression inhibited the aggressiveness of the PDAC cells, suggesting that miR-30a-3p acts as a tumor-suppressive miRNA in PDAC cells. We further identified 102 putative targets of miR-30a-3p regulation in PDAC cells by combining in silico analysis with gene expression data. Of these, ten genes (EPS8, HMGA2, ENDOD1, SLC39A10, TGM2, MGLL, SERPINE1, ITGA2, DTL, and UACA) were independent prognostic factors in multivariate analysis of survival of patients with PDAC (p < 0.01). We also investigated the oncogenic function of the integrin ITGA2 in PDAC cell lines. The integrin family comprises cell adhesion molecules expressed as heterodimeric, transmembrane proteins on the surface of various cells. Overexpression of ITGA2/ITGB1 (an ITGA2 binding partner) was detected in the PDAC clinical specimens. The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.

| S-EPMC7555373 | biostudies-literature

Regulation of Oncogenic Targets by Tumor-Suppressive miR-150-3p in Lung Squamous Cell Carcinoma.

Project description:Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the "cell cycle" based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells.

| S-EPMC8698895 | biostudies-literature

A common MicroRNA signature consisting of miR-133a, miR-139-3p, and miR-142-3p clusters bladder carcinoma in situ with normal umbrella cells.

Project description:miRNAs are small noncoding RNAs with critical roles in a large variety of biological processes such as development and tumorigenesis. miRNA expression profiling has been reported to be a powerful tool to classify tissue samples, including cancers, based on their developmental lineage. In this study, we have profiled the expression of miRNAs in bladder carcinoma in situ (CIS) and distinct cell compartments of the normal bladder, namely umbrella and basal-intermediate urothelial cells, as well as the muscularis propria. We identified several miRNAs differentially expressed between umbrella and basal-intermediate cells (miR-133a, miR-139-3p, miR-142-3p, miR-199b-5p, and miR-221). In situ hybridization confirmed the expression of miR-133a and miR-139-3p in umbrella cells, and miR-142-3p in basal-intermediate cells. Strikingly, miRNA expression levels of CIS most closely resembled the miRNA profile of umbrella cells. Finally, we examined well-established umbrella and basal-intermediate cell immunohistochemical biomarkers in an independent series of CIS samples. Again, this analysis revealed the significant expression of umbrella-specific markers in CIS when compared to non-CIS lesions. Overall, our studies represent a comprehensive and accurate description of the different miRNAs expressed in CIS tumors and three distinct histological areas of the urinary bladder. Notably, this study provides evidence of the possible origin relationship between CIS and normal umbrella cells.

| S-EPMC3620415 | 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