The pseudogene PRELID1P6 promotes glioma progression via the hnHNPH1-Akt/mTOR axis.
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ABSTRACT:
SUBMITTER: Xi S
PROVIDER: S-EPMC8249232 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RNF7 has been reported to play critical roles in various cancers. However, the underlying mechanisms of RNF7 in glioma development remain largely unknown. Herein, the expression level of RNF7 was examined in tissues by quantitative real-time PCR, Western blotting and immunohistochemistry. The effect of RNF7 on glioma progression was measured by performing CCK-8 and apoptosis assays, cell cycle-related experiments and animal experiments. The effect of RNF7 on PI3K/AKT signalling pathway was tested by Western blotting. First, we found that RNF7 was upregulated in tumour tissue compared with normal brain tissue, especially in high-grade glioma, and the high expression of RNF7 was significantly related to tumour size, Karnofsky Performance Scale score and a poor prognosis. Second, RNF7 overexpression facilitated tumour cell cycle progression and cell proliferation and suppressed apoptosis. Conversely, RNF7 knockdown suppressed tumour cell cycle progression and cell proliferation and facilitated apoptosis. Furthermore, follow-up mechanistic studies indicated that RNF7 could facilitate glioma cell proliferation and cell cycle progression and inhibit apoptosis by activating the PI3K/AKT signalling pathway. This study shows that RNF7 can clearly promote glioma cell proliferation by facilitating cell cycle progression and inhibiting apoptosis by activating the PI3K/AKT signalling pathway. Targeting the RNF7/PI3K/AKT axis may provide a new perspective on the prevention or treatment of glioma.
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Project description:Background and Aims: Emerging studies have determined that the small leucine-rich proteoglycan (SLRP) family can aggravate tumor progression. However, the biological function of podocan-like protein 1 (PODNL1), a novel member of the SLRP family, has not been investigated. Therefore, our study focused on the function and regulatory mechanism of PODNL1 in glioma. Methods: Both the Gene Expression Profiling Interactive Analysis (GEPIA) and the Chinese Glioma Genome Atlas (CGGA) database were used to analyze the expression level and survival risk of PODNL1 in glioma. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to detect the mRNA and protein expression, respectively. Celltiter-Glo and colony formation assays were used to evaluate cell proliferation. Migration capacity was measured by Transwell and wound healing assays. Flow cytometry was utilized to assess the apoptotic rate. Results: The expression of PODNL1 predicted the poor prognosis in glioma patients. Silencing of PODNL1 inhibited cell proliferation, migration, and induced epithelial-like phenotype. In addition, knockdown of PODNL1 also induced cell apoptosis. Moreover, the cell growth and migration inhibited by PODNL1 knockdown could be partially rescued with Akt activator. Conversely, PODNL1 overexpression promoted cell growth and migration, which were suppressed by Akt inhibitor. Conclusions: PODNL1, a promising predictive indicator of poor prognosis, resulted in greater proliferation, migration and epithelial-mesenchymal transition (EMT) process. Moreover, PODNL1 promoted aggressive glioma behavior by activating Akt/mTOR pathway, providing a novel therapeutic target for glioma.
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Project description:BackgroundA number of JmjC domain-containing histone demethylases have been identified and biochemically characterized in mammalian models and humans. JMJD2A is a transcriptional co-factor and enzyme that catalyzes the demethylation of histone H3 lysine 9 and 36 (H3K9 and H3K36). Here in this study, we reported the role of JMJD2A in human glioma.MethodsQuantitative real-time PCR and western blot were performed to analyzed JMJD2A expression in glioma. Log-rank was performed to plot the survival curve. JMJD2A was knocked or overexpressed with lentivirus. Cell proliferation and colony formation were performed to assess the effects of JMJD2A on glioma cell growth. Xenograft experiment was performed the evaluate the growth rate of glioma cells in vivo. The signaling pathway was analyzed with western blot and mTOR was inhibited with rapamycin.ResultsQuantitative real-time PCR and western blot experiments revealed higher expression of JMJD2A and lower levels of H3K9me3/H3K36me3 in glioma tissues than that in normal brain tissues. We showed that knockdown of JMJD2A expression attenuated the growth and colony formation in three lines of glioma cells (U251, T98G, and U87MG), whereas JMJD2A overexpression resulted in opposing effects. Furthermore, we performed in vivo xenograft experiments and our data demonstrated that JMJD2A knockdown reduced the growth of glioma T98G cells in vivo. Further mechanism study implicated that JMJD2A activated the Akt-mTOR pathway and promoted protein synthesis in glioma cells via promoting phosphoinositide-dependent kinase-1 (PDK1) expression. The activation of the Akt-mTOR pathway was also validated in human glioma tissues. Finally, we showed that inhibition of mTOR with rapamycin blocked the effects of JMJD2A on protein synthesis, cell proliferation and colony formation of glioma cells.ConclusionsThese findings demonstrated that JMJD2A regulated glioma growth and implicated that JMJD2A might be a promising target for intervention.
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Project description:BackgroundAlthough the availability of therapeutic options including temozolomide, radiotherapy and some target agents following neurosurgery, the prognosis of glioma patients remains poor. Thus, there is an urgent need to explore possible targets for clinical treatment of this disease.MethodsTissue microarrays and immunohistochemistry were used to detect FKBP10, Hsp47, p-AKT (Ser473), p-CREB (Ser133) and PCNA expression in glioma tissues and xenografts. CCK-8 tests, colony formation assays and xenograft model were performed to test proliferation ability of FKBP10 in glioma cells in vitro and in vivo. Quantitative reverse transcriptase-PCR, western-blotting, GST-pull down, co-immunoprecipitation and confocal-immunofluorescence staining assay were used to explore the molecular mechanism underlying the functions of overexpressed FKBP10 in glioma cells.ResultsFKBP10 was highly expressed in glioma tissues and its expression was positively correlates with grade, poor prognosis. FKBP10-knockdown suppressed glioma cell proliferation in vitro and subcutaneous/orthotopic xenograft tumor growth in vivo. Silencing of FKBP10 reduced p-AKT (Ser473), p-CREB (Ser133), PCNA mRNA and PCNA protein expression in glioma cells. FKBP10 interacting with Hsp47 enhanced the proliferation ability of glioma cells via AKT-CREB-PCNA cascade. In addition, correlation between these molecules were also found in xenograft tumor and glioma tissues.ConclusionsWe showed for the first time that FKBP10 is overexpressed in glioma and involved in proliferation of glioma cells by interacting with Hsp47 and activating AKT-CREB-PCNA signaling pathways. Our findings suggest that inhibition of FKBP10 related signaling might offer a potential therapeutic option for glioma patients.
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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.
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Project description:BackgroundDenticleless E3 ubiquitin protein ligase homolog (DTL) has been reported to be an important regulator for tumorigenesis and progression. Nonetheless, the biological functions and molecular mechanisms of DTL in BCa remain elusive.MethodsWe implemented integrative bioinformatics analysis to explore the diagnostic and prognostic values of DTL based on The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene Expression Omnibus (GEO) databases. Then, we utilized qRT-PCR and immunohistochemistry to verify the clinical significance of DTL expression according to clinical specimens and tissue microarray (TMA). Moreover, the biological functions and underlying mechanisms of DTL in BCa were investigated through in vitro and in vivo experiments.ResultsIntegrative bioinformatics analysis revealed that DTL was a key gene associated with BCa progression, and increased DTL expression was correlated with malignant biological behavior and poor prognosis. Experiments on clinical specimens and tissue microarray (TMA) further confirmed our findings. Bioinformatics analysis demonstrated that DTL could be associated with cell cycle- and DNA replication-associated pathways in BCa. The suppression of DTL inhibited BCa cell proliferation, migration, and invasion in vivo and in vitro. Mechanistically, DTL may promote BCa progression through the AKT/mTOR pathway.ConclusionsIncreased DTL expression was correlated with malignant biological behavior and poor prognosis of BCa patients, and it may promote BCa progression through the AKT/mTOR pathway. Our research provided a potential predictor and therapeutic target for BCa.
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