Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study aims to investigate whether circ-HIPK3 could promote the proliferation and invasion of glioma cells by upregulating STAT3 after binding to miR-124-3p, thus participating in the development of glioma. Expression levels of circ-HIPK3, miR-124-3p and STAT3 in glioma cell lines were determined using qRT-PCR. The regulatory effects of circ-HIPK3, miR-124-3p and STAT3 on proliferative and invasive capacities of glioma cells were accessed using EdU assay, CCK-8 assay and invasion assay, respectively. Cell cycle assay and cell apoptosis assay were performed by flow cytometry. Dual-luciferase reporter gene assay was conducted to determine the binding condition among circ-HIPK3, miR-124-3p and STAT3. Rescue experiments were performed in co-transfected glioma cells. QRT-PCR data showed that circ-HIPK3 and STAT3 are highly expressed, whereas miR-124-3p is lowly expressed in glioma cells than those of negative control cell. Knockdown of circ-HIPK3 in U87 and U251 cells inhibited their proliferative and invasive capacities. On the contrary, miR-124-3p knockdown improved proliferative and migratory capacities. Dual-luciferase reporter gene assay exerted that circ-HIPK3 could bind to miR-124-3p and STAT3 is the target gene of miR-124-3p. Western blot results elucidated that circ-HIPK3 stabilizes STAT3 expression, whereas miR-124-3p degrades STAT3 expression. Rescue experiments demonstrated that overexpression of circ-HIPK3 could partially reverse the inhibited proliferative and migratory capacities induced by miR-124-3p in U87 and U251 cells. In summary, we found that overexpression of circ-HIPK3 promotes proliferative and invasive capacities of glioma cells by sponging miR-124-3p to upregulate STAT3 expression.
...
PMID:Circular RNA HIPK3 promotes glioma progression by binding to miR-124-3p. 3057 8

Background: The resistance of glioma patients to temozolomide (TMZ) treatment is a limiting factor in clinical treatment. Circular RNA HIPK3 (circ-HIPK3) was found to be highly expressed in glioma, however, the role and potential mechanism of exosomal circ-HIPK3 from TMZ-resistant cells remain poorly unclear. Methods: Exosomes were characterized by transmission electron microscopy. The levels of all protein were detected by western blot. Expression levels of circ-HIPK3, microRNA-421 (miR-421), and zinc finger protein of the cerebellum 5 (ZIC5) were measured by quantitative real-time polymerase chain reaction. The cell's 50% inhibitory concentration (IC50) of TMZ, apoptosis, and invasion were determined by methyl thiazolyl tetrazolium (MTT), flow cytometry, and Transwell assays, respectively. The correlation between miR-421 and circ-HIPK3 or ZIC5 was identified by dual-reporter luciferase and RNA immunoprecipitation (RIP) assays. The xenograft model was established to explore the effect of circ-HIPK3 in vivo. Results: Circ-HIPK3 was obviously increased in TMZ-resistant glioma cells and their exosomes, miR-421, was downregulated in TMZ-resistant glioma. Circ-HIPK3 directly targeted miR-421 and their expressions were negatively correlated in glioma tissues. Besides, circ-HIPK3 knockdown hampered the IC50 of TMZ, cell invasion, TMZ resistance, and triggered cell apoptosis, whereas these effects were reversed by transfection of anti-miR-421. ZIC5 was the target of miR-421 and ZIC5 overexpression weakened the inhibition effects of miR-421 on cell progression and TMZ resistance. More importantly, circ-HIPK3 depletion inhibited tumor growth by decreasing ZIC5 through sponging miR-421 in vivo. Conclusion: Exosomal circ-HIPK3 could promote cell progression and TMZ resistance by regulating miR-421/ZIC5 axis in TMZ-resistant glioma.
...
PMID:Exosomal Circ-HIPK3 Facilitates Tumor Progression and Temozolomide Resistance by Regulating miR-421/ZIC5 Axis in Glioma. 3264 21

Objective To investigate the effect of circular RNA homeodomain-interacting protein kinase 3 (circHIPK3) on the proliferation and metastasis of glioma cells via sponging miR-124-3p. Methods T98G cells were transfected with circHIPK3 short hairpin RNA (sh-circHIPK3), pcDNA3.1-circHIPK3, miR-124-3p mimics or pcDNA3.1-WEE1 using LipofectamineTM 3000 reagent following the manufacturer's instructions. Real-time quantitative PCR was performed to evaluate the expression of circHIPK3 and miR-124-3p in glioma tissues and cell lines. CCK-8 assay was employed to assess the proliferation of T98G cells. TranswellTM assay was applied to validate the invasion of T98G cells. The targeting relationship among miR-124-3p, circHIPK3 and serine/threonine kinase WEE1 were verified by dual-luciferase reporter gene assay. The expression of WEE1 and epithelial mesenchymal transition (EMT)-related factors (E-cadherin, N-cadherin and vimentin) were measured by Western blot analysis. In addition, after the competitive binding of circHIPK3 and WEE1 to miR-124-3p, the proliferation of T98G cells was detected by CCK-8 assay; the invasion of T98G cells was evaluated by TranswellTM assay. Results The circHIPK3 was upregulated in glioma tissues and cell lines. Knockdown of circHIPK3 repressed the proliferation, invasion and EMT of T98G cells. Dual-luciferase reporter gene assay confirmed that miR-124-3p was the target gene of circHIPK3, while WEE1 was the target gene of miR-124-3p. The miR-124-3p was over-expressed simultaneously with circHIPK3 or WEE1. Co-transfected sh-circHIPK3 and pcDNA3.1-WEE1 restored the inhibitory effect of miR-124-3p overexpression on the proliferation, invasion and EMT of T98G cells. Conclusion The circRNA-HIPK3 and WEE1 can promote the proliferation, invasion and EMT of glioma cells by sponging miR-124-3p.
...
PMID:[Circular RNA homeodomain-interacting protein kinase 3 (circHIPK3) promotes growth and metastasis of glioma cells by sponging miR-124-3p]. 3272 45

As a malignant tumor of the central nervous system, glioma exhibits high incidence and poor prognosis. Circular RNA HIPK3 (circHIPK3) is a circular RNA (circRNA) related to cancer progression. However, the role of circHIPK3 in gliomas remains unclear. The purpose of this study was to investigate the role of circHIPK3 in gliomas and its mechanism. The qRT-PCR method was used to determine the expression pattern of circHIPK3 in glioma cell lines. CCK-8 assay was used to detect cell proliferation. Cell migration and invasion were evaluated using the Transwell assay. Our results showed that circHIPK3 expression was significantly up-regulated in glioma tissues and cell lines. In vitro, the down-regulation of circHIPK3 significantly inhibited the proliferation, migration and invasion of glioma cells. Besides, we demonstrated that circHIPK3 acted as a sponge to absorb miR-124 and promoted CCND2 expression. In summary, our results indicated that circHIPK3 had carcinogenic effects by regulating the expression of CCND2 in glioma by sponging miR-124. These findings provided favorable evidence to reveal the role of circHIPK3 in the development of gliomas.
...
PMID:Circular RNA CircHIPK3 Elevates CCND2 Expression and Promotes Cell Proliferation and Invasion Through miR-124 in Glioma. 3300 82