TUSC3 suppresses glioblastoma development by inhibiting Akt signaling

Jiang, Zhenfeng; Guo, Mian; Zhang, Xiangtong; Yao, Lifen; Shen, Jia; Ma, Guizhen; Liu, Li; Zhao, Lu; Xie, Chuncheng; Liang, Hongsheng; Wang, Haiyang; Zhu, Minwei; Hu, Li; Shen, Hong; Lin, Zhiguo

doi:10.1007/s13277-016-5072-4

Cited by 19 publications

(25 citation statements)

References 48 publications

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“…SPINK6 could be a prognostic indicator in nasopharyngeal carcinoma patients, and SPINK6 could play a critical role in promoting metastasis of nasopharyngeal carcinoma patients [50]. Moreover, TUSC3 was reported to related to the development of different cancers, such as glioblastoma, colorectal cancer, pancreatic cancer, and so on [51–53]. No items of LOC100128054 and C8orf22 were found from pubmed.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Zhang

Dang

et al. 2016

Cancer Cell Int

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BackgroundLong noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown.MethodsHOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve.ResultsAmong the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663–0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906–0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = −0.124, P = 0.048) and lung adenocarcinoma (r = −0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA.Conclus...

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Zhang

Dang

et al. 2016

Cancer Cell Int

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“…Conversely, genes with known tumor-suppressor properties were identified among the genes overexpressed in Tum LOW cells (e.g. TUSC3 [34], SERPINB1 [31]). The whole workflow is summarized in Fig.…”

Section: Gbm Cell Grouping According To Their Tumorigenic Potential Umentioning

confidence: 99%

Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells

Saurty

Bellenger

El-Habr

et al. 2019

Preprint

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Glioblastoma cell ability to adapt their functioning to microenvironment changes is a source of the extensive intra-tumor heterogeneity characteristic of this devastating malignant brain tumor. A systemic view of the metabolic pathways underlying glioblastoma cell functioning states is lacking.We analyzed public single cell RNA-sequencing data from glioblastoma surgical resections, which offer the closest available view of tumor cell heterogeneity as encountered at the time of patients' diagnosis. Unsupervised analyses revealed that information dispersed throughout the cell transcript repertoires encoded the identity of each tumor and masked information related to cell functioning states. Data reduction based on an experimentally-defined signature of transcription factors overcame this hurdle. It allowed cell grouping according to their tumorigenic potential, regardless of their tumor of origin. The approach relevance was validated using an independent dataset of glioblastoma tissue transcriptomes, patient-derived cell lines and orthotopic xenografts.Overexpression of genes coding for amino acid and lipid metabolism enzymes involved in antioxidative, energetic and cell membrane processes characterized cells with high tumorigenic potential. Modeling of their expression network highlighted the very long chain polyunsaturated fatty acid synthesis pathway at the core of the network. Expression of its most downstream enzymatic component, ELOVL2, was associated with worsened patient survival, and required for cell tumorigenic properties in vivo. Our results demonstrate the power of signature-driven analyses of single cell transcriptomes to obtain an integrated view of metabolic pathways at play within the heterogeneous cell landscape of patient tumors.

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“…STn is a truncated O-glycan containing a sialic acid α-2,6 linked to GalNAc α-O-Ser/Thr and has been shown to promote tumour growth and metastasis in mouse models (Julien et al 2006, Ozaki et al 2012. In prostate cancer, the sTn antigen is detected in up to half of all high-grade tumours (Myers et al 1994, Genega et al 2000, and (Kratochvilova et al 2015), pancreatic cancer (Fan et al 2016), glioblastoma (Jiang et al 2016). Overexpressed in colorectal cancer cells -induces EMT, tumour growth and invasion (Gu et al 2016) Downregulated in prostate cancer tissue -acts as a tumour suppressor (Horak et al 2012(Horak et al , 2014 N-glycan processing EDEM3 Mannose trimming of N-glycans Not reported in other cancers Upregulated in malignant PCa as part of a glycosylation gene signature (Barfeld et al 2014a).…”

Section: :3mentioning

confidence: 99%

“…Upregulation of the RPN2 subunit is linked to malignancy and confers resistance to docetaxel in breast cancer (Honma et al 2008, Tominaga et al 2014. In contrast, the TUSC3 subunit has been identified as a tumour suppressor in several cancer types (Kratochvilova et al 2015, Fan et al 2016, Jiang et al 2016. Although there is no reported evidence to date linking RPN2 or STT3A to prostate cancer, TUSC3 has been shown to act as a tumour suppressor in prostate cancer cells and is downregulated in prostate tumours (Horak et al 2012(Horak et al , 2014.…”

Section: N-glycan Biosynthesis (Ost Complex N-glycan Processing)mentioning

confidence: 99%

Glycosylation is a global target for androgen control in prostate cancer cells

Munkley¹

2017

Endocrine-Related Cancer

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Changes in glycan composition are common in cancer and can play important roles in all of the recognised hallmarks of cancer. We recently identified glycosylation as a global target for androgen control in prostate cancer cells and further defined a set of 8 glycosylation enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly upregulated in prostate cancer tissue. These 8 enzymes are under direct control of the androgen receptor (AR) and are linked to the synthesis of important cancer-associated glycans such as sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulfate. Glycosylation has a key role in many important biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism. Our results suggest that alterations in patterns of glycosylation via androgen control might modify some or all of these processes in prostate cancer. The prostate is an abundant secretor of glycoproteins of all types, and alterations in glycans are, therefore, attractive as potential biomarkers and therapeutic targets. Emerging data on these often overlooked glycan modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer.

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TUSC3 suppresses glioblastoma development by inhibiting Akt signaling

Cited by 19 publications

References 48 publications

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells

Glycosylation is a global target for androgen control in prostate cancer cells

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