PSMA2 promotes glioma proliferation and migration via EMT.

BACKGROUND: Gliomas advance rapidly and are associated with a poor prognosis. Epithelial-mesenchymal transition (EMT) accelerates the progression of gliomas, exerting a pivotal role in glioma development. Proteasome subunit alpha type-2 (PSMA2) exhibits high expression levels in gliomas. however, its specific involvement in glioma progression and its correlation with EMT remain elusive. This study aims to elucidate the role of PSMA2 in glioma progression and its potential association with EMT. METHODS: Online tools were employed to analyze the expression patterns and survival curves of PSMA2 in gliomas. The relationship between PSMA2 and various characteristics of glioma patients was investigated using data from the TCGA and CGGA databases. In vitro, cell proliferation and migration were assessed through CCK-8, colony formation, and transwell assays. Furthermore, a tumor xenograft model in nude mice was established to evaluate in vivo tumorigenesis. Protein binding to PSMA2 was scrutinized using co-immunoprecipitation MS (co-IP MS). The potential biological functions and molecular pathways associated with PSMA2 were explored through GO analysis and KEGG analysis, and the correlation between PSMA2 and EMT was validated through correlation analysis and Western blot experiments. RESULTS: Bioinformatics analysis revealed a significant upregulation of PSMA2 across various cancers, with particularly heightened expression in gliomas. Moreover, elevated PSMA2 levels were correlated with advanced tumor stages and diminished survival rates among glioma patients. Inhibition of PSMA2 demonstrated a pronounced suppressive effect on glioma cell proliferation, both in vitro and in vivo. Knockdown of PSMA2 also impeded the migratory capacity of glioma cells. GO and KEGG enrichment analyses indicated that PSMA2-binding proteins (identified through Co-IP-MS) were associated with cell adhesion molecule binding and cadherin binding. Western blot results further confirmed the role of PSMA2 in promoting epithelial-mesenchymal transition (EMT) in glioma cells. CONCLUSION: Our study provides evidence supporting the role of PSMA2 as a regulatory factor in EMT and suggests its potential as a prognostic biomarker for glioma progression.

Long non-coding RNA DDX11-AS1 promotes the proliferation and migration of glioma cells by combining with HNRNPC.

Glioma is a malignant tumor of the central nervous system with complex pathogenesis, difficult operation, and a high postoperative recurrence rate. At present, there is still a lack of effective treatment. Long non-coding RNA DDX11 antisense RNA 1 (DDX11-AS1) has been shown to promote tumor development, such as hepatocellular carcinoma, esophageal cancer, etc. However, its molecular mechanism in glioma is poorly understood. In this study, we found that the expression of DDX11-AS1 was elevated in glioma tissues, and patients with high expression of DDX11-AS1 had poor prognosis. DDX11-AS1 was a potential prognostic marker. Functionally, DDX11-AS1 promoted glioma cell proliferation and migration. Mechanistically, DDX11-AS1 interacted with RNA-binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) to promote Wnt/ß-catenin and AKT pathways and the epithelial-mesenchymal transition process. In summary, our study manifests that the DDX11-AS1/HNRNPC axis may play a vital part in the occurrence and development of glioma, which provides new ideas and therapeutic targets for the diagnosis, treatment, and prognosis of glioma.

Identification and Validation of an Endoplasmic Reticulum Stress-Related lncRNA Signature for Colon Adenocarcinoma Patients.

Purpose: Endoplasmic reticulum (ER) stress has a significant effect on cancer cells. Increasing numbers of studies indicate that long non-coding RNAs (lncRNAs) promote the development of colon adenocarcinoma (COAD), but the relationship between ER stress-related lncRNAs and the prognosis of COAD remains unclear. The aim of the current study was to construct and validate an ER stress-related lncRNA prognostic signature to predict COAD prognoses. Methods: Gene expression data and clinical information from the Cancer Genome Atlas and the Gene Expression Omnibus with COAD were downloaded and analyzed. Cox regression and least absolute shrinkage and selection operator regression were then used to develop an ER stress-related lncRNA signature. COAD patients were then divided into high-risk and low-risk groups based on the median risk score to analyze prognoses. Tumor mutation burdens (TMBs) and the differences in copy number variations (CNVs) between the two groups were also analyzed. Lastly, gene set enrichment analysis (GSEA) was used to explore the enrichment pathways and biological processes associated with differentially expressed genes in the high-risk and low-risk groups, and lncRNA expression in the model was validated via quantitative real-time PCR in colon cancer and paracancerous tissues. Results: A signature including 8 ER stress-related lncRNAs was constructed. COAD prognoses were significantly poorer in the high-risk group than in the low-risk group. There were few differences in TMBs and CNVs between the two groups. In GSEA analysis, in the high-risk group highly expressed genes associated with extracellular matrix pathways were significantly enriched. Conclusion: The 8-ER stress-related lncRNA derived from the present study is a potential indicator of COAD prognosis.

Genome-wide analysis of valine-glutamine motif-containing proteins related to abiotic stress response in cucumber (Cucumis sativus L.).

BACKGROUND: Cucumber (Cucumis sativus L.) is one of the most important economic crops and is susceptible to various abiotic stresses. The valine-glutamine (VQ) motif-containing proteins are plant-specific proteins with a conserved "FxxhVQxhTG" amino acid sequence that regulates plant growth and development. However, little is known about the function of VQ proteins in cucumber. RESULTS: In this study, a total of 32 CsVQ proteins from cucumber were confirmed and characterized using comprehensive genome-wide analysis, and they all contain a conserved motif with 10 variations. Phylogenetic tree analysis revealed that these CsVQ proteins were classified into nine groups by comparing the CsVQ proteins with those of Arabidopsis thaliana, melon and rice. CsVQ genes were distributed on seven chromosomes. Most of these genes were predicted to be localized in the nucleus. In addition, cis-elements in response to different stresses and hormones were observed in the promoters of the CsVQ genes. A network of CsVQ proteins interacting with WRKY transcription factors (CsWRKYs) was proposed. Moreover, the transcripts of CsVQ gene were spatio-temporal specific and were induced by abiotic adversities. CsVQ4, CsVQ6, CsVQ16-2, CsVQ19, CsVQ24, CsVQ30, CsVQ32, CsVQ33, and CsVQ34 were expressed in the range of organs and tissues at higher levels and could respond to multiple hormones and different stresses, indicating that these genes were involved in the response to stimuli. CONCLUSIONS: Together, our results reveal novel VQ resistance gene resources, and provide critical information on CsVQ genes and their encoded proteins, which supplies important genetic basis for VQ resistance breeding of cucumber plants.

APMAP Promotes Epithelial-Mesenchymal Transition and Metastasis of Cervical Cancer Cells by Activating the Wnt/ß-catenin Pathway.

Cervical cancer is a malignant tumor of the female reproductive system. At present, its occurrence, development and transfer mechanism are not entirely clear. APMAP (Adipocyte Plasma Membrane Associated Protein) is a glycosyl type II transmembrane protein that is mainly distributed in the plasma membrane and endoplasmic reticulum of adipocytes. APMAP has been reported to be involved in lipid transport and can induce epithelial-mesenchymal transition of prostate cancer and the liver metastasis of colorectal cancer. However, the role of APMAP in cervical cancer is still unknown. We analyzed the expression and prognosis of APMAP using data in both the GEO and the TCGA databases. We analyzed the function of APMAP using Transwell, wound healing assay and flow cytometry, and assessed the main mechanisms of APMAP by RT-PCR and Western blotting. We found that APMAP was highly expressed in cervical cancer tissues, and patients with high expression had poor prognosis. The functional in vitro experiments demonstrated that APMAP knockdown significantly inhibited the migration ability of cervical cancer cells, but had little effect on cell apoptosis. Mechanically, APMAP promotes cervical cancer cell migration and epithelial-mesenchymal transition by activating the Wnt/ß-catenin pathway. Overall, APMAP is a potential prognostic marker as well as a therapeutic target of cervical cancer.

A Novel Inflammatory lncRNAs Prognostic Signature for Predicting the Prognosis of Low-Grade Glioma Patients.

BACKGROUND: As immunotherapy has received attention as new treatments for brain cancer, the role of inflammation in the process of glioma is of particular importance. Increasing studies have further shown that long non-coding RNAs (lncRNAs) are important factors that promote the development of glioma. However, the relationship between inflammation-related lncRNAs and the prognosis of glioma patients remains unclear. The purpose of this study is to construct and validate an inflammation-related lncRNA prognostic signature to predict the prognosis of low-grade glioma patients. METHODS: By downloading and analyzing the gene expression data and clinical information of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) patients with low-grade gliomas, we could screen for inflammatory gene-related lncRNAs. Furthermore, through Cox and the Least Absolute Shrinkage and Selection Operator regression analyses, we established a risk model and divided patients into high- and low-risk groups based on the median value of the risk score to analyze the prognosis. In addition, we analyzed the tumor mutation burden (TMB) between the two groups based on somatic mutation data, and explored the difference in copy number variations (CNVs) based on the GISTIC algorithm. Finally, we used the MCPCounter algorithm to study the relationship between the risk model and immune cell infiltration, and used gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the enrichment pathways and biological processes of differentially expressed genes between the high- and low-risk groups. RESULTS: A novel prognostic signature was constructed including 11 inflammatory lncRNAs. This risk model could be an independent prognostic predictor. The patients in the high-risk group had a poor prognosis. There were significant differences in TMB and CNVs for patients in the high- and low-risk groups. In the high-risk group, the immune system was activated more significantly, and the expression of immune checkpoint-related genes was also higher. The GSEA, GO, and KEGG analyses showed that highly expressed genes in the high-risk group were enriched in immune-related processes, while lowly expressed genes were enriched in neuromodulation processes. CONCLUSION: The risk model of 11 inflammation-related lncRNAs can serve as a promising prognostic biomarker for low-grade gliomas patients.

ACTL6A knockdown inhibits cell migration by suppressing the AKT signaling pathway and enhances the sensitivity of glioma cells to temozolomide.

Molecular-targeted therapy has had a significant impact on glioma. Notably, actin-like 6A (ACTL6A) has been indicated to be essential for embryonic development and tumor progression. However, the role of ACTL6A in glioma remains unclear. The present study aimed to investigate the effects of ACTL6A on glioma cell migration and sensitivity to temozolomide (TMZ). The expression levels of ACTL6A were analyzed in patients with glioma, and survival curves were created using data from The Cancer Genome Atlas. U251 and T98G cells were transfected with short hairpin (sh)RNA for use in loss-of-function experiments to investigate the biological function and molecular mechanisms of ACTL6A. Furthermore, an MTT assay was used to assess the effect of ACTL6A on the sensitivity of glioma cells to TMZ. The results demonstrated that ACTL6A was expressed at higher levels in glioma tissues compared with normal brain tissues. Furthermore, high expression of ACTL6A was associated with a poor prognosis. The knockdown of ACTL6A significantly inhibited the migration phenotype in glioma cells and significantly decreased the levels of phosphorylated AKT in glioma cells. The AKT signaling activator SC79 partly attenuated the inhibitory effects of ACTL6A shRNA on glioma cell migration. Additionally, the knockdown of ACTL6A enhanced the sensitivity of glioma cells to TMZ. In conclusion, these results suggest that ACTL6A knockdown inhibited the migration of human glioma cells, at least in part through inactivation of the AKT signaling pathway, and increased the sensitivity of glioma cells to TMZ. Therefore, ACTL6A may be a potential therapeutic target for glioma.

A seven-gene signature model predicts overall survival in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a potentially fatal urogenital disease. It is a major cause of renal cell carcinoma and is often associated with late diagnosis and poor treatment outcomes. More evidence is emerging that genetic models can be used to predict the prognosis of KIRC. This study aimed to develop a model for predicting the overall survival of KIRC patients. RESULTS: We identified 333 differentially expressed genes (DEGs) between KIRC and normal tissues from the Gene Expression Omnibus (GEO) database. We randomly divided 591 cases from The Cancer Genome Atlas (TCGA) into training and internal testing sets. In the training set, we used univariate Cox regression analysis to retrieve the survival-related DEGs and futher used multivariate Cox regression with the LASSO penalty to identify potential prognostic genes. A seven-gene signature was identified that included APOLD1, C9orf66, G6PC, PPP1R1A, CNN1G, TIMP1, and TUBB2B. The seven-gene signature was evaluated in the training set, internal testing set, and external validation using data from the ICGC database. The Kaplan-Meier analysis showed that the high risk group had a significantly shorter overall survival time than the low risk group in the training, testing, and ICGC datasets. ROC analysis showed that the model had a high performance with an AUC of 0.738 in the training set, 0.706 in the internal testing set, and 0.656 in the ICGC external validation set. CONCLUSION: Our findings show that a seven-gene signature can serve as an independent biomarker for predicting prognosis in KIRC patients.

Lnc GNG12-AS1 knockdown suppresses glioma progression through the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly being regarded as regulators of glioma development. Notably, some studies report that GNG12-AS1 plays important functions and molecular mechanism in breast cancer, but there are no existing studies in glioma. OBJECTIVE: To analyze the biological functions and potential mechanisms of GNG12-AS1 in glioma. METHODS: We detected the expression of GNG12-AS1 in glioma tissues through analyzing TCGA data as well as our clinical samples. We then evaluated cell proliferation through MTT assay and colony formation and cell migration by transwell assay, wound healing assay and single cell tracking assay. After, we analyzed the effects of the AKT/GSK-3ß/ß-catenin through Western blotting and utilized the ß-catenin agonist SKL2001 for the rescue experiment. RESULTS: GNG12-AS1 was highly expressed in glioma tissues. The silence of GNG12-AS1 inhibited the proliferation, migration and epithelial-mesenchymal transition of glioma cells, and reduced the activity of the AKT/GSK-3ß/ß-catenin pathway. Notably, SKL2001 could reverse cell migration as well as ß-catenin expression in glioma cells with lower GNG12-AS1 expression. CONCLUSIONS: GNG12-AS1 regulates proliferation and migration of glioma cells through the AKT/GSK-3ß/ß-catenin signaling and can perhaps be a new target for the treatment of glioma.