Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR-RAS–MAPK signaling pathway

Kang, Aram; An, Hyoung-Tae; Ko, Jesang; Choi, Eui-Ju; Kang, Seongman

doi:10.18632/oncotarget.21814

Cited by 22 publications

(24 citation statements)

References 44 publications

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“…4 F ). A link between ataxin-1 and cell proliferation has been recently described, and mitogen-activated protein kinase (MAPK) signaling was shown to be critical in mediating this function ( 22 ). The “regulation of MAPK cascade” term was found enriched also in our GO analysis, supporting its possible involvement in B cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis

Didonna

Puig

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Ataxin-1 (ATXN1) is a ubiquitous polyglutamine protein expressed primarily in the nucleus where it binds chromatin and functions as a transcriptional repressor. Mutant forms of ataxin-1 containing expanded glutamine stretches cause the movement disorder spinocerebellar ataxia type 1 (SCA1) through a toxic gain-of-function mechanism in the cerebellum. Conversely, ATXN1 loss-of-function is implicated in cancer development and Alzheimer’s disease (AD) pathogenesis. ATXN1 was recently nominated as a susceptibility locus for multiple sclerosis (MS). Here, we show that Atxn1-null mice develop a more severe experimental autoimmune encephalomyelitis (EAE) course compared to wildtype mice. The aggravated phenotype is mediated by increased T helper type 1 (Th1) cell polarization, which in turn results from the dysregulation of B cell activity. Ataxin-1 ablation in B cells leads to aberrant expression of key costimulatory molecules involved in proinflammatory T cell differentiation, including cluster of differentiation (CD)44 and CD80. In addition, comprehensive phosphoflow cytometry and transcriptional profiling link the exaggerated proliferation of ataxin-1 deficient B cells to the activation of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT) pathways. Lastly, selective deletion of the physiological binding partner capicua (CIC) demonstrates the importance of ATXN1 native interactions for correct B cell functioning. Altogether, we report a immunomodulatory role for ataxin-1 and provide a functional description of the ATXN1 locus genetic association with MS risk.

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Section: Resultsmentioning

confidence: 99%

Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis

Didonna

Puig

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, ATXN1 is a component of the Notch signaling pathway [ 22 ], and the Notch signaling reportedly mediates tumor cell migration and invasion induced by low oxygen supply (hypoxia), which is a critical characteristic of solid tumors [ 23 ]. Previous studies have demonstrated that a potential link between ATXN1 expression (both upregulation and downregulation) and cancer development in humans could regulate cell proliferation and the epithelial-mesenchymal transition of cells in various cancers [ 24 , 25 ], but it remains unknown whether ATXN1 acts as a tumor suppressor or an oncogene. Therefore, the ATXN1 might play an important role in the OSCC.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0008309 May Be a Potential Biomarker for Oral Squamous Cell Carcinoma

Wang

et al. 2018

Disease Markers

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Objective Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear. Methods 8 pairs of OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by high-throughput sequencing, and 45 pairs of OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa_circ_0008309, the circRNA-microRNA (miR)-mRNA network was predicted using bioinformatics databases. The expression levels of hsa_circ_0008309, miR-1290, miR-136-5P, and miR-382-5P in SCC-15 and CAL27 cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein level of Ataxin 1 (ATXN1). Results The high-throughput sequencing results demonstrated that circRNAs were abundantly expressed in OSCC, and 16 circRNAs were significantly differentially expressed. Hsa_circ_0008309 was significantly downregulated in 45 pairs of OSCC tissue samples and was statistically correlated with pathological differentiation. The bioinformatics databases suggested that hsa_circ_0008309 could combine with miR-1290, miR-136-5P, and miR-382-5P, respectively, to regulate the expression of ATXN1. It was subsequently identified that hsa_circ_0008309 may inhibit miR-136-5P and miR-382-5P expression and increase ATXN1 expression in the OSCC cell lines. Conclusion In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, we firstly explore the regulatory role of the hsa_circ_0008309-miR-136-5P/hsa-miR-382-5P-ATXN1 network in OSCC. The results indicated that hsa_circ_0008309 may be a potential biomarker for OSCC.

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“…In addition to highlighting known cancer genes, uKIN also ranks highly several non-CGC genes that may or may not play a functional role in cancer, as our knowledge of cancer-related genes is incomplete. Among these novel predictions for GBM are ATXN1, SMURF1, and CCR3, all of which have been recently suggested to play a role in cancers [45][46][47] and are each mutated in less than 5% of the samples. ATXN1 is a chromatin-binding factor that plays a critical role in the development of spinocerebellar ataxia, a neurodegenerative disorder [48], and mutants of ATXN1 have been found to stimulate the proliferation of cerebellar stem cells in mice [49].…”

Section: Resultsmentioning

confidence: 99%

A Guided Network Propagation Approach to Identify Disease Genes that Combines Prior and New Information

Hristov

Chazelle

Singh

2020

Lecture Notes in Computer Science

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A major challenge in biomedical data science is to identify the causal genes underlying complex genetic diseases. Despite the massive influx of genome sequencing data, identifying disease-relevant genes remains difficult as individuals with the same disease may share very few, if any, genetic variants. Protein-protein interaction networks provide a means to tackle this heterogeneity, as genes causing the same disease tend to be proximal within networks. Previously, network propagation approaches have spread "signal" across the network from either known disease genes or genes that are newly putatively implicated in the disease (e.g., found to be mutated in exome studies or linked via genome-wide association studies). Here we introduce a general framework that considers both sources of data within a network context. Specifically, we use prior knowledge of disease-associated genes to guide random walks initiated from genes that are newly identified as perhaps disease-relevant. In large-scale testing across 24 cancer types, we demonstrate that our approach for integrating both prior and new information not only better identifies cancer driver genes than using either source of information alone but also readily outperforms other state-of-the-art network-based approaches. To demonstrate the versatility of our approach, we also apply it to genome-wide association data to identify genes functionally relevant for several complex diseases. Overall, our work suggests that guided network propagation approaches that utilize both prior and new data are a powerful means to identify disease genes.

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Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR-RAS–MAPK signaling pathway

Cited by 22 publications

References 44 publications

Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis

Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis

Hsa_circ_0008309 May Be a Potential Biomarker for Oral Squamous Cell Carcinoma

A Guided Network Propagation Approach to Identify Disease Genes that Combines Prior and New Information

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