The involvement of the circFOXM1-miR-432-Gα12 axis in glioma cell proliferation and aggressiveness.
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ABSTRACT:
SUBMITTER: Gong Y
PROVIDER: S-EPMC8748925 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hepatocellular carcinoma (HCC) predominantly occurs in patients with chronic liver disease, accounting for 70-90% of all liver cancer cases. The role of circFOXM1/miR-1179/SPAG5 axis in HCC has not been reported. This study aimed to explore the regulatory mechanism of circFOXM1 in HCC proliferation and metastasis. RNA polymerase inhibitor actinomycin D and RNase R exonuclease were used to identify circFOXM1 in HCC cells. The qRT-PCR was used to detect circFOXM1 expression. Specific siRNA for circFOXM1 was designed, and the sequence of circFOXM1 was inserted in pLCDH-ciR to overexpress circFOXM. Cell proliferation was detected by CCK8 in vitro, by tumor volume and tumor weight of HCC xenograft in vivo. Cell migration was detected by transwell test. Binding status of circFOXM1 with miR-1179 was detected by luciferase reporter gene assay. Rescue experiments were applied to identify the oncogenic mechanism of circFOXM1 in HCC cells. Actinomycin D assay confirmed the cyclization of circFOXM1. RNase R treatment showed that circFOXM1 was not affected by RNase R exonuclease. CCK8 assay, tumor volume and tumor weight showed that circFOXM1 effectively promoted HCC cell proliferation. Transwell assay showed that circFOXM effectively promoted migration and invasion abilities of HCC cells. Luciferase reporter gene activity assay showed that miR-1179 had complementary binding sites with circFOXM1 and SPAG5. CircFOXM1 silencing inhibited malignant phenotypes in HCC cells were partly rescued by either miR-1179 silencing or SPAG5 overexpression. CircFOXM1 promoted HCC cell proliferation and metastasis by regulating miR-1179/SPAG5 axis.
| S-EPMC8668908 | biostudies-literature
Project description:Glioma is a malignant brain cancer that exhibits high invasive ability and poor prognosis. MicroRNA (miR)‑181d has been reported to be involved in the development of glioma. Therefore, the aim of the present study was to investigate whether miR‑181d affected cellular progression by influencing the insulin like growth factor (IGF1)/PI3K/AKT axis. Western blot analysis was performed to analyze the expression levels of specific proteins, and a Cell Counting Kit‑8 assay was used to assess the proliferative ability of cells. Cell cycle progression and cellular apoptosis were both measured using flow cytometry. The results indicated that miR‑181d promoted cellular proliferation and cell cycle progression, while suppressing cellular apoptosis via the IGF1/PI3K/AKT axis. It was demonstrated that the IGF1 and PI3K/AKT inhibitors reversed these observed functions of miR‑181d. Furthermore, miR‑181d enhanced the growth of glioma xenografts in vivo, promoted cell cycle progression and suppressed cellular apoptosis within glioma xenograft tissues. Therefore, this newly identified miR‑181d/IGF1/PI3K/AKT axis may provide novel insights into the pathogenesis of glioma.
| S-EPMC7533453 | biostudies-literature
Project description:Gliomas are the most common primary tumors in the brain with poor prognosis. Previous studies have detected high expression of Cyclophilin A (CyPA) and CD147, respectively, in glioma. However, the correlation between their expressions and glioma prognosis remains unclear. Here, we investigated the expression of CyPA and CD147 in different types of glioma and characterized their relationships with clinical features, prognosis, and cell proliferation. Results showed that CyPA and CD147 expressions were elevated in higher grade gliomas. Moreover, the knockdown of CyPA and CD147 by RNA interference significantly induced cell express apoptosis biomarkers such as Annexin V and inhibited proliferation biomarkers like EdU in glioma cells. In summary, our findings revealed that high expression of CyPA and CD147 correlated with glioma grades. Moreover, downregulation of the Cyclophilin A/CD147 axis induces cell apoptosis and inhibits glioma aggressiveness. Those indicating CyPA and CD147 could be used as both potential predictive biomarkers and a potential therapeutic target.
| S-EPMC7396009 | biostudies-literature
Project description:Glioma is the most common primary intracranial malignant tumour in adults. It has a high incidence and poses a serious threat to human health. Circular RNA is a hotspot of cancer research. In this study, we aimed to explore the role of circ_0001367 in gliomagenesis and the underlying mechanism. First, qRT-PCR was conducted, which showed that circ_0001367 level was downregulated in glioma tissues and cells. Next, gain-of-function and loss-of-function assays were performed, which indicated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells. Subsequent bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation assays and cell function assays demonstrated that circ_0001367 inhibited the proliferation, migration and invasion of glioma cells by absorbing miR-545-3p and thereby regulating the expression of leucine zipper protein (LUZP1). Finally, an in vivo experiment was conducted, which demonstrated that circ_0001367 inhibited glioma growth in vivo by modulating miR-545-3p and LUZP1. Taken together, the results of this study demonstrate that the circ_0001367/miR-545-3p/LUZP1 axis may be a novel target for glioma therapy.
| S-EPMC8637337 | biostudies-literature
Project description:Accumulating evidence suggests that microRNAs (miRNAs) play a key role in the biological behaviors and progression of glioma. However, the function and bio?molecular mechanisms of miR?342 in glioma remain largely unclear. In the present study, reverse transcription quantitative?polymerase chain reaction and western blotting were performed to determine the mRNA and protein expression levels of the factors investigated. MTT assay was performed to examine the proliferation rates. Luciferase reporter assay was performed to test the binding between miRNA?342 and its putative target. Data indicated that miR?342 expression was markedly decreased in human glioma tissues and cell line U87, and reduced miR?342 expression significantly promoted cell proliferation. In order to explore the mechanisms, G?protein coupled receptor family C group 5 member A (GPRC5A) was identified as a target of miR?342 and depletion of GPRC5A suppressed cell proliferation. Our findings demonstrated that miR?342 regulates the cell proliferation of glioma by targeting GPRC5A, which indicates that miR?342 is a target of interest regarding the treatment of refractory glioma, and it may provide a promising prognostic and therapeutic strategy for glioma treatment.
| S-EPMC6579993 | biostudies-literature
Project description:UnlabelledAtypical protein kinase C-iota (PKC-iota) protects cells against apoptosis and may play a role in cell proliferation. However, in vivo, the status and function of PKC-iota in human normal brain tissue, gliomas, benign and malignant meningiomas as well as its in vitro status in proliferating and confluent glioma cells, remains unknown.ObjectivesThe objectives of our research were to determine whether expression of PKC-iota is altered either in gliomas or in benign and malignant meningiomas, compared to normal brain. In addition, we wished to establish the expression of PKC-iota in proliferating plus in cell cycle-arrested glioma cell lines, as well as the relationship between PKC-iota siRNA on PKC-iota protein content and cell proliferation.Materials and methodsWestern blot analyses for PKC-iota were performed on 12 normal brain biopsies, 15 benign meningiomas, three malignant meningiomas and three gliomas.ResultsResults demonstrated no (n = 9) or very weak (n = 3) detection of PKC-iota in normal brain tissue. In comparison, PKC-iota was robustly present in the majority of the benign meningiomas. Similarly, PKC-iota was abundant in all malignant meningiomas and gliomas. Western blotting for PKC-iota in confluent or proliferating glioma cell lines depicted substantial quantities of PKC-iota in proliferating T98G and U-138MG glioma cells. In contrast, confluent cells had either 71% (T98G) or 21% (U-138MG) less PKC-iota than proliferating cells. T98 and U-138 MG glioma cells treated with 100 nm PKC-iota siRNA had lower levels of cell proliferation compared to control siRNA-A and complete down-regulation of PKC-iota protein content.ConclusionThese results support the concept that presence of PKC-iota may be required for cell proliferation to take place.
| S-EPMC6496708 | biostudies-literature
Project description:Background:Long noncoding RNAs (lncRNAs) are recognized as key effectors in tumor, including glioma. LINC01494 is an uncharacterized novel lncRNA. In this research, we aimed to investigate the function of LINC01494 in glioma. Methods:Gene relative expression was analyzed by qRT-PCR method. CCK8, colony formation and Transwell assay was used to determine cell proliferation, migration and invasion. Bioinformatics analyses were used to predict the target of LINC01494 and miR-122-5p. Luciferase reporter assay was utilized to validate the interactions between LINC01494 and miR-122-5p or CCNG1 and miR-122-5p. Results:LINC01494 was identified as a significantly upregulated lncRNA in glioma through bioinformatics analysis. Furthermore, LINC01494 upregulation indicated poor prognosis. Meanwhile, in vitro investigation indicated that silencing LINC01494 with siRNAs obviously inhibited the proliferation, cell cycle, migration and invasion of glioma cells. Besides, it is found that LINC01494 expression was negatively correlated with miR-122-5p. We demonstrated that LINC01494 inhibited miR-122-5p to upregulate CCNG1 expression through direct interaction. Rescue assay further demonstrated that LINC01494/miR-122-5p/CCNG1 signaling cascade plays a critical role in regulating glioma cell proliferation, migration and invasion. Conclusion:Taken together, our findings demonstrated the essential function and molecular mechanism of LINC01494 in glioma progression.
| S-EPMC6756415 | biostudies-literature
Project description:Glioma is a prevalent brain malignancy with aggressive progression and with grave prognosis in adults. Circular RNAs have been reported to regulate glioma development and function as the diagnostic, prognostic, and therapeutic biomarkers. In this study, we were interested the function of circular RNA ZNF609 in modulating glioma. Remarkably, knockdown of ZNF609 by siRNA in glioma cells reduced cell viabilities and Edu-positive. The silencing of ZNF609 stimulated the apoptosis of glioma cells. Meanwhile, the ZNF609 depletion inhibited the invasion and migration of glioma cells. In glioma cells, the mRNA and protein expression of E-cadherin was enhanced, while Vimentin was reduced by the inhibition of ZNF609. The glucose uptake, lactate product, and ATP production in glioma cells were suppressed by ZNF609 knockdown. Mechanically, miR-378b was sponged by ZNF609 and targeted SLC2A1 in glioma cells. ZNF609 enhanced SLC2A1 expression by inhibiting miR-378b. The inhibition of miR-378b or the enhancement of SLC2A1 reversed ZNF609 depletion-regulated glioma cell proliferation in vitro. The depletion of ZNF609 suppressed glioma cell growth in the nude mice. Therefore, we concluded that ZNF609 contributed to cell survival and glycolysis of glioma by targeting miR-378b/SLC2A1 axis. ZNF609 and miR-378b may function as potential treatment targets in glioma.
| S-EPMC8457557 | biostudies-literature
Project description:Sustained cell growth and proliferation, one of the hallmarks of cancer, is considered to responsible for cancer-related deaths by disorganizing the balance of growth promotion and growth limitation. Aberrant activation of the Wnt/?-catenin signaling pathway leads to cell proliferation, growth and survival, and promotes the development of various human tumors, including hepatocellular carcinoma. Elucidating the molecular mechanism of this abnormality in hepatocellular carcinoma carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. Herein, we report that the expression of miR-432 was markedly downregulated in hepatocellular carcinoma cell lines and tissues, and upregulation of miR-432 inhibited, whereas downregulation of miR-432 enhanced the proliferation and tumorigenicity of hepatocellular carcinoma cells both in vitro and in vivo. Furthermore, miR-432 directly targeted and suppressed multiple regulators of the Wnt/?-catenin signaling cascade, including LRP6, TRIM29 and Pygo2, which subsequently deactivated Wnt/?-catenin signaling pathway. Finally, miR-432 expression was inversely correlated with three targets in clinical hepatocellular carcinoma samples. These results demonstrated that miR-432 functions as a tumor-suppressive miRNA by suppressing Wnt/?-catenin signaling activation and may represent a therapeutic target for hepatocellular carcinoma.
| S-EPMC4480722 | biostudies-literature
Project description:BackgroundAs a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. However, the functions of different circRNAs in gliomas remain elusive.MethodsThe levels of circRNAs, miRNAs, and mRNAs were quantified by qPCR. The interaction between circDENND2A and miR-625-5p was determined by luciferase reporter and pull-down assays. The migratory and invasive capabilities of glioma cells were examined by wound healing and Transwell assays. Immunohistochemistry was performed to analyze the HIF1α level in glioma tissues.ResultsWe predicted circDENND2A (has_circ_0002142) to be a hypoxia-responsive circRNA in glioma via a bioinformatic analysis. We found that hypoxia induced the expression of circDENND2A, which promoted migration and invasion of glioma cells. To understand the behaviors of circDENND2A in glioma, we studied the putative miRNAs targeted by circDENND2A and identified circDENND2A as an efficient sponge of miR-625-5p in glioma cells. Phenotype experiments verified that circDENND2A was required for the hypoxia-induced migration and invasion of glioma cells and that this occurred by sponging of miR-625-5p. Notably, glioma tissues overexpressing HIF1α exhibited a high expression of circDENND2A as well as a low expression of miR-625-5p. circDENND2A was negatively correlated with miR-625-5p.ConclusioncircDENND2A is required for the hypoxia-induced malignancy of glioma cells and functions by sponging miR-625-5p.
| S-EPMC6446274 | biostudies-literature