The high expression of TC1 (C8orf4) was correlated with the expression of β-catenin and cyclin D1 and the progression of squamous cell carcinomas of the tongue

Zhang, Peng; Cao, Hongyan; Bai, Linlin; Li, Weinan; Wang, Yuan; Chen, Songyan; Zhang, Li; Yang, Lianhe; Xu, Hong‐Tao; Wang, Enhua

doi:10.1007/s13277-015-3423-1

Cited by 14 publications

(21 citation statements)

References 28 publications

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“…For example, Chromosome 8 Open Reading Frame 4 (C8orf4), ranked 9th by NMF, was identified as “ Thyroid cancer 1 (TC1)” (Panebianco et al, 2015; Zhang et al, 2015; Zhu et al, 2015; Huang et al, 2016). Epidermal Growth Factor Receptor (EGFR), a gene ranked 31st by NMF, has elevated expression from MGH29 to MGH31.…”

Section: Resultsmentioning

confidence: 99%

Detecting heterogeneity in single-cell RNA-Seq data by non-negative matrix factorization

Zhu

Ching

Pan

et al. 2017

PeerJ

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Single-cell RNA-Sequencing (scRNA-Seq) is a fast-evolving technology that enables the understanding of biological processes at an unprecedentedly high resolution. However, well-suited bioinformatics tools to analyze the data generated from this new technology are still lacking. Here we investigate the performance of non-negative matrix factorization (NMF) method to analyze a wide variety of scRNA-Seq datasets, ranging from mouse hematopoietic stem cells to human glioblastoma data. In comparison to other unsupervised clustering methods including K-means and hierarchical clustering, NMF has higher accuracy in separating similar groups in various datasets. We ranked genes by their importance scores (D-scores) in separating these groups, and discovered that NMF uniquely identifies genes expressed at intermediate levels as top-ranked genes. Finally, we show that in conjugation with the modularity detection method FEM, NMF reveals meaningful protein-protein interaction modules. In summary, we propose that NMF is a desirable method to analyze heterogeneous single-cell RNA-Seq data. The NMF based subpopulation detection package is available at: https://github.com/lanagarmire/NMFEM.

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Section: Resultsmentioning

confidence: 99%

Detecting heterogeneity in single-cell RNA-Seq data by non-negative matrix factorization

Zhu

Ching

Pan

et al. 2017

PeerJ

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“…Several studies reported high expression levels of TC1 across a wide range of tumors, and a positive association with malignancy [ 10 , 13 , 17 – 19 , 23 , 24 ]. However, reduced expression of TC1 was observed in colon cancer tumors relative to normal mucosa [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that TC1 promotes tumor development primarily by enhancing the activity of the Wnt/β-catenin signaling pathway [ 10 , 13 , 19 , 23 ]. However, the relationship between TC1 and other key members of the Wnt/β-catenin signaling pathway is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Although originally identified in papillary thyroid cancer, TC1 is ubiquitously expressed in human tissues [ 2 ]. Studies have shown that TC1 expression levels positively correlates with development of many malignancies including thyroid cancer [ 1 , 17 ], gastric cancer [ 10 ], breast cancer [ 13 ], ovarian carcinomas [ 18 ], oral tongue squamous cell carcinomas [ 19 ], and hematological malignancies [ 20 , 21 ]. Expression levels of TC1 correlate with poor clinical outcome and decreased survival in patients with gastric cancer and hematological malignancies [ 10 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

et al. 2017

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Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. β-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined. Bisulfite sequencing PCR analysis was used to examine the methylation status of the C8orf4 locus, while PCR analysis and direct sequencing were used to determine its mutational status. We found high TC1 expression correlated with poor differentiation, advanced TNM stage, lymphatic metastasis, and poor prognosis in lung cancer patients. TC1 expression also correlated with β-catenin and DNMT1 expressions. No mutations in C8orf4 were detected. However, methylation levels of C8orf4 in lung cancers were lower than in corresponding normal lung tissues. In conclusion, high TC1 expression is implicated in lung cancer progression and correlates with poor prognosis in lung cancer. Reduced methylation levels might be responsible for the elevated TC1 expression levels. TC1, β-catenin, and DNMT1 can synergistically activate Wnt/β-catenin signaling in lung cancers.

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“…In 299 gastric cancers, TC-1 expression was in correlation with a subset of β-catenin target genes, including laminin γ2, metalloproteinase-7 and metalloproteinase-14, cyclin D1, c-Met, and CD44 ( Kim et al, 2006a ). High expression of TC-1 was common in 109 cases of oral tongue squamous cell carcinomas (OTSCCs) and correlated with the expression of β-catenin and cyclin D1, indicating the carcinogenesis of TC-1 in OTSCCs by enhancing the activity of Wnt/β-catenin signaling pathway ( Zhang et al, 2015 ). TC-1 was also observed in 97 of the 147 primary tumor specimens of NSCLC, and it was correlated with the TNM stage as well as regional lymph node metastasis, which was in line with the results of in vitro experiments demonstrating that it promoted the proliferation and invasion of lung cancer cells through Wnt/β-catenin signaling pathway ( Su et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of TC-1 enhances radiosensitivity of non-small cell lung cancer via the Wnt/β-catenin pathway

Yan

2016

Biology Open

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Thyroid cancer 1 (TC-1, C8ofr4) is widely expressed in vertebrates and associated with many kinds of tumors. Previous studies indicated that TC-1 functions as a positive regulator in the Wnt/β-catenin signaling pathway in non-small cell lung cancer (NSCLC). However, its exact role and regulation mechanism in radiosensitivity of NSCLC are still unclear. The expression level of TC-1 was measured by qRT-PCR and western blot in NSCLC cell lines. Proliferation and apoptosis of NSCLC cells in response to TC-1 knockdown or/and radiation were determined by MTT assay and flow cytometry, respectively. The activation of the Wnt/β-catenin signaling pathway was further examined by western blot in vitro and in vivo. Compared to TC-1 siRNA or radiotherapy alone, TC-1 silencing combined with radiation inhibited cell proliferation and induced apoptosis in NSCLC cell lines by inactivating of the Wnt/β-catenin signaling pathway. Furthermore, inhibition of the Wnt/β-catenin signaling pathway by XAV939, a Wnt/β-catenin signaling inhibitor, contributed to proliferation inhibition and apoptosis induction in NSCLC A549 cells. Combinative treatment of A549 xenografts with TC-1 siRNA and radiation caused significant tumor regression and inactivation of the Wnt/β-catenin signaling pathway relative to TC-1 siRNA or radiotherapy alone. The results from in vitro and in vivo studies indicated that TC-1 silencing sensitized NSCLC cell lines to radiotherapy through the Wnt/β-catenin signaling pathway.

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The high expression of TC1 (C8orf4) was correlated with the expression of β-catenin and cyclin D1 and the progression of squamous cell carcinomas of the tongue

Cited by 14 publications

References 28 publications

Detecting heterogeneity in single-cell RNA-Seq data by non-negative matrix factorization

Detecting heterogeneity in single-cell RNA-Seq data by non-negative matrix factorization

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with β-catenin and DNMT1 expression and poor prognosis

Knockdown of TC-1 enhances radiosensitivity of non-small cell lung cancer via the Wnt/β-catenin pathway

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