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HMGA2 promotes glioma invasion and poor prognosis via a long-range chromatin interaction.

ABSTRACT: To identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan-Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP-qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co-immunoprecipitation were applied to identify HMGA2-activated target sites, which were further verified by mRNA and protein expression detection. Transwell and orthotopic implantation were used to investigate the roles of HMGA2 in glioma cells. HMGA2 shRNA transfection inhibited glioblastoma invasion. Mechanistically, we first discovered that HMGA2, together with GCN5, facilitated the invasion of glioma cells via inducing chromatin conformational remodeling of the MMP2 gene promoter and epigenetically activating MMP2 gene transcription. Our results indicated that HMGA2, as a novel GCN5 recognition partner and histone acetylation modulator, may be novel prognostic indicator and promising glioma treatment target.

SUBMITTER: Zhang S

PROVIDER: S-EPMC6051173 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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HMGA2 promotes glioma invasion and poor prognosis via a long-range chromatin interaction.

Zhang Shanshan S Zhang Huibian H Yu Lin L

Cancer medicine 20180507 7

To identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan-Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP-qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co-immunoprecipitation were applied to identify HMGA2-activated target sites, which were further verified by mRNA and protein ex ...[more]

PMID: 29733521

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Project description:BackgroundLINC00324 is a long-stranded non-coding RNA, which is aberrantly expressed in various cancers and is associated with poor prognosis and clinical features. It involves multiple oncogenic molecular pathways affecting cell proliferation, migration, invasion, and apoptosis. However, the expression, function, and mechanism of LINC00324 in glioma have not been reported.Material and methodsWe assessed the expression of LINC00324 of LINC00324 in glioma patients based on data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify pathways involved in LINC00324-related glioma pathogenesis.ResultsBased on our findings, we observed differential expression of LINC00324 between tumor and normal tissues in glioma patients. Our analysis of overall survival (OS) and disease-specific survival (DSS) indicated that glioma patients with high LINC00324 expression had a poorer prognosis compared to those with low LINC00324 expression. By integrating clinical data and genetic signatures from TCGA patients, we developed a nomogram to predict OS and DSS in glioma patients. Gene set enrichment analysis (GSEA) revealed that several pathways, including JAK/STAT3 signaling, epithelial-mesenchymal transition, STAT5 signaling, NF-κB activation, and apoptosis, were differentially enriched in glioma samples with high LINC00324 expression. Furthermore, we observed significant correlations between LINC00324 expression, immune infiltration levels, and expression of immune checkpoint-related genes (HAVCR2: r = 0.627, P = 1.54e-77; CD40: r = 0.604, P = 1.36e-70; ITGB2: r = 0.612, P = 6.33e-7; CX3CL1: r = -0.307, P = 9.24e-17). These findings highlight the potential significance of LINC00324 in glioma progression and suggest avenues for further research and potential therapeutic targets.ConclusionIndeed, our results confirm that the LINC00324 signature holds promise as a prognostic predictor in glioma patients. This finding opens up new possibilities for understanding the disease and may offer valuable insights for the development of targeted therapies.

Project description:Background: The long non-coding RNA Linc00152 stimulates tumor progression in cancer. However, its clinical significance and biological functions in lung adenocarcinoma remains unknown. We evaluate the expression of Linc00152 in lung adenocarcinoma and its possible correlation with clinicopathologic features and patient survival to reveal its biological effects in cancer progression and prognosis. Methods: Total RNA extraction was performed on 110 pairs of lung adenocarcinoma and adjacent normal tissue samples, and then RT-qPCR was conducted. Chi-square test analysis was used to calculate the correlation between pathological parameters and the Linc00152 mRNA levels. Kaplan-Meier and Cox proportional hazards analyses were used to analyze the overall survival (OS) and disease-free survival (DFS) rates. We also detected the potential functional effects of overexpression and knockdown of Linc00152 in vitro cell proliferation, tumor cell invasion and migration, as well as in vivo nude mouse xenograft and metastasis models. Results: The Linc00152 expression levels were higher in lung adenocarcinoma samples than in the adjacent normal tissues. Linc00152 expression levels tightly correlated with lymph node metastasis station, remote metastasis and TNM staging. The Kaplan-Meier analysis suggested that high Linc00152 expression caused significantly poorer OS and DFS rates, and a multivariate analysis revealed that Linc00152 was an independent risk factor for both DFS and OS. Overexpression of Linc00152 in lung cancer cells stimulated proliferation, tumor cell invasion and migration. Knockdown of Linc00152 inhibited cell growth and cell invasion and migration. Finally, Linc00152 knockdown inhibited lung tumor growth and tumor metastasis in nude mice models. Conclusions: Our study suggests that Linc00152 independently predicts poor prognosis and promotes tumor progression in lung adenocarcinoma. Linc00152 needs to be considered as a potential molecular target in future cancer pharmacology.

Dataset Information

HMGA2 promotes glioma invasion and poor prognosis via a long-range chromatin interaction.

Publications

HMGA2 promotes glioma invasion and poor prognosis via a long-range chromatin interaction.

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