Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis.

ABSTRACT: Colorectal neoplasia differentially expressed (CRNDE) is the most upregulated long noncoding RNA (lncRNA) in glioma. Herein, the function and potential molecular mechanisms of CRNDE and miR-384 were illustrated in glioma cells. CRNDE overexpression facilitated cell proliferation, migration, and invasion, while inhibited glioma cells apoptosis. Quantitative real-time polymerase chain reaction (PCR) demonstrated that miR-384 was downregulated in human glioma tissues and glioma cell lines. Moreover, restoration of miR-384 exerted tumor-suppressive functions. In addition, the expression of miR-384 was negatively correlated with CRNDE expression. A binding region between CRNDE and miR-384 was confirmed using luciferase assays. Moreover, CRNDE promoted cell malignant behavior by decreasing miR-384 expression. At the molecular level, treatment by CRNDE knockdown or miR-384 overexpression resulted in a decrease of piwi-like RNA-mediated gene silencing 4 (PIWIL4) protein. Besides, PIWIL4 was identified as a target of miR-384 and plays an oncogenic role in glioma. Similarly, downstream proteins of PIWIL4 such as STAT3, cyclin D1, VEGFA, SLUG, MMP-9, caspase 3, Bcl-2, and bcl-xL were modulated when treated with miR-384 and PIWIL4. Remarkably, CRNDE knockdown combined with miR-384 overexpression led to tumor regression in vivo. Overall, these results depicted a novel pathway mediated by CRNDE in glioma, which may be a potential application for glioma therapy.

SUBMITTER: Zheng J

PROVIDER: S-EPMC5088760 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

circRNA-0002109 promotes glioma malignant progression via modulating the miR-129-5P/EMP2 axis.

Project description:Glioma is a common intracranial malignant tumor with high mortality and high recurrence rate. In recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) are potential biomarkers and therapeutic targets for many tumors. However, the role of circRNAs in glioma remains unclear. In this study, we found that circRNA-0002109 was highly expressed in glioma tissues and cell lines. Downregulation of circRNA-0002109 expression inhibited the proliferation, migration, and invasion of glioma cells and inhibited the malignant progression of tumors in vivo. Investigations into the relevant mechanisms showed that circRNA-0002109 upregulated the expression of EMP2 through endogenous competitive binding of microRNA-129-5P (miR-129-5P), which partially alleviated the inhibitory effect of miR-129-5P on epithelial membrane protein-2 (EMP2) and ultimately promoted the malignant development of glioma. Our results indicate that circRNA-0002109 plays an important role in the proliferation, invasion, and migration of glioma cells by regulating the miR-129-5P/EMP2 axis, which provides a new potential therapeutic target for glioma.

| S-EPMC8646083 | biostudies-literature

STAT3 Blockade Inhibits Radiation-Induced Malignant Progression in Glioma.

Project description:High grade gliomas (HGG) are classified into four subgroups based on transcriptional signatures and phenotypic characteristics. In particular, the proneural-to-mesenchymal transition (PMT) is associated with increased malignancy, poor prognosis, and disease recurrence, but the underlying causes of PMT are still unclear. In this study, we investigated whether radiotherapy promotes PMT using a genetically engineered mouse model of proneural HGG. We found that cranial ionizing radiation induced robust and durable PMT in tumors. Additionally, we isolated primary proneural HGG cells from mouse and human tumors and demonstrate that radiation induced a sustained cell-intrinsic mesenchymal transition associated with increased invasiveness and resistance to the alkylating agent temozolomide. Expectedly, irradiation-induced PMT was also associated with activation of the STAT3 transcription factor, and the combination of STAT3 blockade using JAK2 inhibitors with radiation abrogated the mesenchymal transition and extended survival of mice. Taken together, our data suggest that clinical JAK2 inhibitors should be tested in conjunction with radiation in patients with proneural HGG as a new strategy for blocking the emergence of therapy-resistant mesenchymal tumors at relapse.

| S-EPMC4609277 | biostudies-literature

LncRNA CRNDE promotes cell proliferation, invasion and migration by competitively binding miR-384 in papillary thyroid cancer.

Project description:Thyroid cancer is one of the most prevalent endocrine neoplasm. The present study examined the effects of Colorectal Neoplasia Differentially Expressed (CRNDE) on the progression of papillary thyroid cancer (PTC), and explored the underlying molecular mechanisms. Quantitative real-time PCR was used to detect CRNDE, miR-384 and pleiotrophin (PTN) mRNA expression. Western blot was used to measure PTN protein levels. Cell proliferation, cell growth, cell invasion and migration of PTC cells were determined by CCK-8, colony formation, transwell invasion and migration assays, respectively. CRNDE was up-regulated in PTC tissues and cell lines. Overexpression of CRNDE promoted BCPAP cell proliferation, invasion and migration, while knock-down of CRNDE suppressed K1 cell proliferation, invasion and migration. CRNDE negatively regulated the expression of miR-384 in PTC cells, which was further confirmed by luciferase reporter assay. MiR-384 was down-regulated and inversely correlated with CRNDE expression in PTC tissues. MiR-384 suppressed cell proliferation, invasion and migration in PTC cells, and enforced expression of miR-384 attenuated the oncogenic effects of CRNDE in PTC cells. PTN was predicted as a downstream target of miR-384, which was confirmed by luciferase reporter assay, and PTN was up-regulated in PTC tissues, and was negatively correlated with miR-384 expression and positively correlated with CRNDE expression in PTC tissues. In summary, our results suggested that the CRNDE/miR-384/PTN axis may play an important role in the regulation of PTC progression, which provides us with new insights into understanding the PTC.

| S-EPMC5746403 | biostudies-literature

Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma.

Project description:Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was upregulated in TMZ-resistant glioma cells and TMZ-resistant glioma cell-derived exosomes compared with their controls by using high-throughput microarray analysis and quantitative real-time polymerase chain reaction, and high circWDR62 expression was associated with poor prognosis of glioma. Functionally, downregulation of circWDR62 expression could significantly inhibit the TMZ resistance and malignant progression of glioma. Further mechanistic studies showed that circWDR62 plays a role by sponging miR-370-3p as a competing endogenous RNA. Rescue experiments confirmed that MGMT is the downstream target of the circWDR62/miR-370-3p axis in glioma. In addition, circWDR62 could be transported between TMZ-resistant and TMZ-sensitive glioma cells via exosomes. Exosomal circWDR62 from TMZ-resistant cells conferred TMZ resistance in recipient sensitive cells while also enhancing the proliferation, migration and invasion of these cells. A series of clinical and in vivo trials corroborated that exosomal circWDR62 could promote TMZ chemoresistance and malignant progression of glioma. Our results demonstrate for the first time that exosome-mediated delivery of circWDR62 can promote TMZ resistance and malignant progression via targeting of the miR-370-3p/MGMT axis in vitro and in vivo in glioma, providing a new therapeutic strategy. Moreover, exosomal circWDR62 in human serum may serve as a promising therapeutic target and prognostic marker for glioma therapy.

| S-EPMC9273787 | biostudies-literature

A proangiogenic signaling axis in myeloid cells promotes malignant progression of glioma.

Project description:Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. Deficiency of ID2 in BMDCs led to downregulation of KDR, suppression of proangiogenic myeloid cells, and prevention of low-grade to high-grade transition. Tumor-secreted TGF-β and granulocyte-macrophage CSF (GM-CSF) enhanced the KDR/ID2 signaling axis in BMDCs. Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas.

| S-EPMC5409793 | biostudies-literature

CircNFIX promotes progression of glioma through regulating miR-378e/RPN2 axis.

Project description:BACKGROUND:Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. METHODS:GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. RESULTS:The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. CONCLUSION:Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.

| S-EPMC6936104 | biostudies-literature

lncRNA CRNDE is Upregulated in Glioblastoma Multiforme and Facilitates Cancer Progression Through Targeting miR-337-3p and ELMOD2 Axis.

Project description:Introduction:Colorectal neoplasia differentially expressed (CRNDE) was reported to promote carcinogenesis in several cancers. However, the role of CRNDE in glioblastoma multiforme (GBM) needs to be further explored. Methods:CRNDE expression levels in GBM tissues and cells were explored using real-time quantitative PCR at first. Effects of CRNDE on GBM cell behaviors were detected by conducting in vitro experiments. Interactions of CRNDE, microRNA-337-3p (miR-337-3p), and ELMO domain containing 2 (ELMOD2) were verified by bioinformatics analysis tools and dual-luciferase reporter assay. Expression correlations of CRNDE and ELMOD2 in GBM tissues were analyzed at GEPIA website. Results:CRNDE expression was upregulated in GBM tissues and cells compared with normal counterparts. CRDNE knockdown inhibits proliferation and migration, but promotes apoptosis in GBM cell, while CRNDE overexpression caused opposite effects. Mechanisms exploration indicated CRNDE serves as sponge of miR-337-3p to upregulate ELMOD2 expression. Furthermore, we showed CRNDE and ELMOD2 were positively correlated in GBM tissues. Discussion:In conclusion, our study highlighted the importance of CRNDE/miR-337-3p/ELMOD2 axis in GBM progression and offered novel strategies for GBM treatment.

| S-EPMC7502397 | biostudies-literature

Circular RNA circitga7 accelerates glioma progression via miR-34a-5p/VEGFA axis.

Project description:Circular RNAs (circRNAs) are a group of noncoding RNAs derived from back-splicing events. CircRNA is reported to be involved in various tumor progressions, including glioma. Although there are a few reports of circular RNAs participating in gliomas, it is still unclear whether circular RNAs regulate the occurrence of gliomas. In our research, we found that the expression of circITGA7 in glioma tissues and glioma cells increased significantly. Knocking down circITGA7 can significantly inhibit the proliferation of glioma cells and reduce cell metastasis. Through analysis and dual-luciferase report assay, we found that circITGA7 acts as a sponge for miR-34a-5p targeting VEGFA in glioma. Our study showed that circITGA7 regulates the proliferation and metastasis of glioma cell lines (SW1783&U373) by regulating the miR-34a-5p/VEGFA pathway. In conclusion, our study revealed a regulatory loop for the circITGA7/miR-34a-5p/VEGFA axis to regulate glioma development.

| S-EPMC8148479 | biostudies-literature

Circ_0005576 Promotes Malignant Progression Through miR-874/CDK8 Axis in Colorectal Cancer.

Project description:Purpose:To investigate the function of circ_0005576 in colorectal cancer (CRC) progression. Patients and Methods:Circ_0005576 expression in CRC patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). CRC cells were transfected using Lipofectamine 2000 reagent. CRC cell proliferation was researched by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2-deoxy-uridine (EdU) incorporation experiment. Cell cycle and apoptosis were determined by flow cytometry analysis. Luciferase reporter assay was used to explore the relationship between circ_0005576 and miR-874 or between miR-874 and CDK8. qRT-PCR and Western blot were used to detect circ_0005576, miR-874, and CDK8 expression. In vivo experiments were performed using nude mice. CDK8 and Ki67 expression in xenograft tumors was investigated by immunohistochemistry. Tunel assay was conducted to analyze the apoptosis of xenograft tumors. Results:Circ_0005576 expression was up-regulated in CRC, which was associated with tumor progression (P < 0.05 or P < 0.01). Circ_0005576 knockdown in CRC cells reduced proliferation, induced apoptosis, increased cells in the G1 phase, and decreased cells in the S phase (P < 0.01 or P < 0.001). Circ_0005576 promoted CDK8 expression via sponging miR-874. miR-874 knockdown and CDK8 overexpression significantly reversed the inhibitory effect of circ_0005576 knockdown on CRC cells malignant phenotype (P < 0.05 or P < 0.01). Circ_0005576 knockdown inhibited tumor growth in vivo (P < 0.01). Circ_0005576 knockdown reduced CDK8, Ki67 expression, and enhanced apoptosis in xenograft tumors. Conclusion:Circ_0005576 promoted malignant progression through the miR-874/CDK8 axis in CRC.

| S-EPMC7430768 | biostudies-literature

The STAT3-miR-223-TGFBR3/HMGCS1 axis modulates the progression of cervical carcinoma.

Project description:Cervical cancer is induced by persistent infections with high-risk human papillomaviruses (HPVs), which produce the early protein 6 of HPVs (E6)/E7 protein that is involved in cell transformation by interacting with several oncoproteins or tumor suppressors. However, the role of noncoding RNA in mediating the pathogenesis of cervical cancer remains unclear. Here, we report that the novel signal transducer and activator of transcription 3 (STAT3)-microRNA-223-3p (miR-223)-TGFBR3/HMGCS1 axis regulated by the E6 protein controls cervical carcinogenesis. miR-223 was highly expressed in cervical tumor tissues, whereas TGFBR3 or HMGCS1 was significantly downregulated. miR-223 targeted the 3'-UTRs of TGFBR3 and HMGCS1 and suppressed their expression, leading to increased anchorage-independent growth and cervical squamous cell carcinoma (CSCC) tumor growth in vitro and in vivo. The increased expression of miR-223 was mediated by the transcription factor STAT3, whose activity was enhanced by E6 in the context of interleukin (IL)-6 stimulation. In addition, exosomal miR-223 derived from CSCC cells induced IL-6 secretion by monocyte/macrophage in a coculture system in vitro, and IL-6 secretion, in turn, led to enhanced STAT3 activity in CSSC cells, forming a positive feedback loop. Furthermore, modified miR-223 inhibitor effectively suppressed tumor growth in cell line-derived xenograft model, suggesting that miR-223 is a potential promising therapeutic target in CSCC. In conclusion, our results demonstrate that the STAT3-miR-223-HMGCS1/TGFBR3 axis functions as a key signaling pathway in cervical cancer progression and provides a new therapeutic target.

| S-EPMC7463355 | 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