Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3.
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ABSTRACT:
SUBMITTER: Liu L
PROVIDER: S-EPMC8149867 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Glioma is the most common and aggressive primary brain tumor with high mortality rate around the world. LncRNAs have been identified to play key roles in tumorigenesis in various cancers, including glioma. However, the precise mechanism of DANCR in progression of glioma remains poorly defined. Methods:The expression levels of DANCR, miR-135a-5p and BMI1 were measured by qRT-PCR in glioma tissues and cells. Cell proliferation, migration and invasion were detected by CCK-8 assay and transwell assay, respectively. The possible binding sites of miR-135a-5p and DANCR or BMI1 were predicted by online software and verified using luciferase report assay and RNA immunoprecipitation (RIP) assay. Western blot analysis was carried out to detect the protein of BMI1 expression. A xenograft tumor model was established to investigate the functions of DANCR in glioma progression in vivo. Results:DANCR was upregulated and miR-135a-5p was downregulated in glioma tissues and cells. Knockdown of DANCR inhibited cell proliferation, migration and invasion in glioma cells. In addition, miR-135a-5p was a direct target of DANCR, and its elevated expression could reverse miR-135a-5p inhibition-mediated progression of glioma. Moreover, miR-135a-5p could specially bind to BMI1, and the expression of BMI1 was obviously elevated in glioma tissues and cells. Furthermore, DANCR acted as a ceRNA to regulate BMI1 expression and BMI1-mediated effects on progression of glioma by sponging miR-135a-5p. Besides, inhibition of DANCR limited tumor growth by regulating miR-135a-5p and BMI1 expression in vivo. Conclusion:DANCR knockdown inhibited cell proliferation, migration and invasion in glioma cells through regulating miR-135a-5p/BMI1 axis, providing viable therapeutic avenues for treatment of glioma.
| S-EPMC7029463 | biostudies-literature
Project description:BackgroundThe extraordinary invasive capability is a major cause of treatment failure and tumor recurrence in glioma, however, the molecular and cellular mechanisms governing glioma invasion remain poorly understood. Evidence in other cell systems has implicated the regulatory role of microRNA in cell motility and invasion, which promotes us to investigate the biological functions of miR-124 in glioma in this regard.ResultsWe have found that miR-124 is dramatically downregulated in clinical specimen of glioma and is negatively correlated with the tumor pathological grading in the current study. The cells transfected by miR-124 expression vector have demonstrated retarded cell mobility. Using a bioinformatics analysis approach, rho-associated coiled-coil containing protein kinase 1 (ROCK1), a well-known cell mobility-related gene, has been identified as the target of miR-124. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3'UTR of ROCK1 gene and repressed the ROCK1 expression in U87MG human glioma cell line. Furthermore, experiments have shown that the decreased cell mobility was due to the actin cytoskeleton rearrangements and the reduced cell surface ruffle in U87MG glioma cells. These results are similar to the cellular responses of U87MG glioma cells to the treatment of Y-27632, an inhibitor of ROCK protein. Moreover, a constitutively active ROCK1 in miR-124 over-expressed glioma cells reversed the effects of miR-124. Our results revealed a novel mechanism that miR-124 inhibits glioma cells migration and invasion via ROCK1 downregulation.ConclusionsThese results suggest that miR-124 may function as anti-migration and anti-invasion influence in glioma and provides a potential approach for developing miR-124-based therapeutic strategies for malignant glioma therapy.
| S-EPMC3720724 | biostudies-literature
Project description:Gliomas are the most common and aggressive type of primary adult brain tumor. Although high expression and prognostic value of TMEM45A has been recently reported in various types of human tumors, the association of TMEM45A expression and glioma is still unknown. Here, we reported that TMEM45A was significantly overexpressed in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM45A mRNA levels were gradually increased with the increasing severity of histological grade of glioma. Moreover, high TMEM45A expression level was correlated with short survival time of glioma patients. Down-regulation of TMEM45A in two glioma cell lines, U251 and U373 by transected with TMEM45A siRNA resulted in a significant reduction of cell proliferation and G1-phase arrest. Additionally, we found that suppressing of TMEM45A expression in glioma cells remarkably suppressed cell migration and cell invasion. More importantly, TMEM45A siRNA treatment significantly down-regulated the proteins promoting cell cycles transition (Cyclin D1, CDK4 and PCNA) and cell invasion (MMP-2 and MMP-9), which indicted a possible mechanism underlying its functions on glioma. In summary, our study suggests that TMEM45A may work as an oncogene and a new effective therapeutic target for glioma treatment.
| S-EPMC4680400 | biostudies-literature
Project description:BACKGROUND:The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS:Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. RESULTS:The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited ?-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. CONCLUSION:Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells.
| S-EPMC3383704 | biostudies-literature
Project description:BackgroundGlioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a dismal prognosis. Despite intensive study on tumor biology, the underlying mechanisms of the unlimited proliferation and progressive local invasion are still poorly understood, and no effective treatment has been developed for GBM patients.AimsWe determine the role of TRPM7 channels in the growth, migration, and infiltration of malignant glioma cells.MethodsUsing a combination of RT-PCR, Western blot, and patch-clamp techniques, we demonstrated the expression of functional TRPM7 channels of A172 cells, a human glioma cell line, as well as in human glioma tissues. Furthermore, we evaluated the role of TRPM7 in growth, migration, and infiltration of A172 cells with MTT and transwell migration and invasion assays.ResultsWe showed the expression of functional TRPM7 channels in both A172 cells and human glioma tissues. Suppression of TRPM7 expression with TRPM7-siRNA dramatically reduced the proliferation, migration, and invasion of A172 cells. Pharmacological inhibition of TRPM7 channel with 2-aminoethoxydiphenyl borate (2-APB) showed a similar effect as TRPM7-siRNA.ConclusionWe demonstrate that human glioma cells express functional TRPM7 channel and that activation of this channel plays an important role in the proliferation, migration, and invasion of malignant glioma cells. TRPM7 channel may represent a novel and promising target for therapeutic intervention of malignant glioma.
| S-EPMC4339490 | biostudies-literature
Project description:E2F3a, as a member of the E2F family, is essential for cell division associated with the progression of many cancers. However, the biological effect of E2F3a on glioma is not understood as well. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissue and cell lines. We found that E2F3a was upregulated in glioma tissue compared with adjacent tissue, and this was associated with a poor survival rate. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines. Knockdown of E2F3a significantly inhibited cell proliferation, promoted G0/G1 phase arrest, elevated apoptosis rates, and suppressed cell migration and invasion. However, overexpression of E2F3a markedly promoted cell proliferation, migration, and invasion and inhibited apoptosis. Moreover, in vivo studies showed that knockdown of E2F3a expression dramatically inhibited U373 tumor growth in a nude mouse model. Results of real-time PCR and Western blot showed that the depletion of E2F3a upregulated the expression levels of cell apoptosis-related proteins and downregulated migration-related proteins. Conversely, E2F3a overexpression downregulated the expression levels of cell apoptosis-related proteins and upregulated migration-related proteins. In conclusion, our results highlight the importance of E2F3a in glioma and provide new insights into the diagnostics and therapeutics of gliomas.
| S-EPMC7841128 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most prevalent type of malignant cancer in the adult central nervous system; however, its mechanism remains unclear. Angiomotin‑like 2 (AMOTL2) is a member of the motin family of angiostatin‑binding proteins. It has been reported as an oncogene in cervical and breast cancer, but its association with glioma remains unknown. The aim of the present study was to investigate AMOTL2‑regulated processes in glioma cell lines using extensive in vitro assays and certain bioinformatics tools. These results revealed that AMOTL2 was downregulated in high‑grade glioma cells and tissues, with patients with glioma exhibiting a high AMOTL2 expression having a higher survival rate. The results of the glioma cell phenotype experiment showed that AMOTL2 suppressed GBM proliferation, migration and invasion. In addition, immunoblotting, co‑immunoprecipitation and immunofluorescence assays demonstrated that AMOTL2 could directly bind to β‑catenin protein, the key molecule of the Wnt signaling pathway, and regulate its downstream genes by regulating β‑catenin nuclear translocation. In conclusion, the present study demonstrated that AMOTL2 inhibited glioma proliferation, migration and invasion by regulating β‑catenin nuclear localization. Thus, AMOTL2 may serve as a therapeutic target to further improve the prognosis and prolong survival time of patients with glioma.
| S-EPMC8165599 | biostudies-literature
Project description:Glioma associates with high malignancy and poor prognosis for traditional treatment. Oleanolic acid (OA) has been confirmed to have an inhibitory effect on different kinds of tumors, while accompanying with low efficiency because of its large molecular mass and low solubility. Nanoliposome is an appropriate drug delivery system that can compensate for the limitations of traditional insoluble drugs, involving improvement of their solubility, stability and lipophilicity. In the present study, we comprised of OA covered with nanoliposomes, named OAnano, to observe antitumor effects on U87 glioma cells. The results showed that OAnano raised the solubility and oil-water partition coefficient. OAnano suppressed proliferation of U87 glioma cells, and also had an anticancer effect on U87 glioma cells, which was found to be higher than that of OA. Moreover, treatment with OAnano induced apoptosis and degraded migration ability by caspase-3 pathway. In conclusion, our results demonstrated that OA covered with nanoliposomes led to enhanced anticancer effects by suppressing proliferation, migration and invasion abilities. The findings may provide a reliable reference for development of new anti-cancer drugs.
| S-EPMC7052863 | biostudies-literature
Project description:BackgroundNon-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gastric cancer (GC). But, the underlying molecular mechanisms by which ncRNAs modulate LATS1 expression in GC remain undetermined.MethodsThe correlation of LATS1 and has-miR-424-5p (miR-424) expression with clinicopathological characteristics and prognosis of GC patients was analyzed by TCGA RNA-sequencing data. A novel circular RNA_LARP4 (circLARP4) was identified to sponge miR-424 by circRNA expression profile and bioinformatic analysis. The binding site between miR-424 and LATS1 or circLARP4 was verified using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The expression and localization of circLARP4 in GC tissues were investigated by fluorescence in situ hybridization (FISH). MTT, colony formation, Transwell and EdU assays were performed to assess the effects of miR-424 or circLARP4 on cell proliferation and invasion.ResultsIncreased miR-424 expression or decreased LATS1 expression was associated with pathological stage and unfavorable prognosis of GC patients. Ectopic expression of miR-424 promoted proliferation and invasion of GC cells by targeting LATS1 gene. Furthermore, circLARP4 was mainly localized in the cytoplasm and inhibited biological behaviors of GC cells by sponging miR-424. The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients.ConclusioncircLARP4 may act as a novel tumor suppressive factor and a potential biomarker in GC.
| S-EPMC5594516 | biostudies-literature
Project description:microRNAs (miRNAs) have been found to affect various cancers, and expression of numerous miRNAs is revealed in glioma. However, the role of microRNA-30b-3p (miR-30b-3p) in glioma remains elusive. Therefore, the present study aims to explore the specific mechanism by which miR-30b-3p influence the development of glioma in relation to the AKT signaling pathway. First, glioma cell lines were collected with miR-30b-3p and reversion-inducing cysteine-rich protein with kazal motifs (RECK) expression measured. The functional role of miR-30b-3p and RECK in glioma was determined via gain- and loss-of-function approaches. Subsequently, the expression of invasion- and migration-related factors (MMP-2 and MMP-9) and the AKT signaling pathway-related factors (AKT, p-AKT and PI3K-p85) was detected. Moreover, in vivo experiments were also conducted to investigate how miR-30b-3p influences in vivo tumorigenesis. The results showed that miR-30b-3p was up-regulated and RECK was down-regulated in glioma. RECK was a target gene of miR-30b-3p. Decreased miR-30b-3p and overexpressed RECK led to decreased expression of MMP-2, MMP-9 and p-AKT. Overexpressed RECK and LY294002 could decrease p-AKT and PI3K-p85 expression accompanied with unchanged expression of total protein of AKT. Additionally, proliferation, migration and invasion of glioma cells and tumor formation in nude mice were repressed owing to reduced expression of miR-30b-3p or elevated expression of RECK. In summary, miR-30b-3p inhibition suppresses metastasis of glioma cells by inactivating the AKT signaling pathway via RECK up-regulation, providing a new target for glioma treatment.
| S-EPMC6692569 | biostudies-literature