Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

2015 ◽  
Vol 11 (3) ◽  
pp. 743-752 ◽  
Author(s):  
Paul Dowling ◽  
Damian Pollard ◽  
AnneMarie Larkin ◽  
Michael Henry ◽  
Paula Meleady ◽  
...  

Role of hnRNPA2B1 in lung cancer.

2021 ◽  
Vol 10 ◽  
Author(s):  
Wei Guo ◽  
Qilin Huai ◽  
Guochao Zhang ◽  
Lei Guo ◽  
Peng Song ◽  
...  

BackgroundLung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein “reader” of N6-methyladenosine (m6A) methylation, and is related to the progression of various cancers; however, its role in LUAD is unclear. The aims of this study aims were to study the expression and prognostic value of HNRNPC in LUAD.MethodsThe Oncomine database and gene expression profiling interactive analysis (GEPIA) were used for preliminary exploration of HNRNPC expression and prognostic value in LUAD. LUAD cases from The Cancer Genome Atlas (TCGA) (n = 416) and the Kaplan-Meier plotter database (n = 720) were extracted to study the differential expression and prognostic value of HNRNPC. HNRNPC expression in the National Cancer Center of China (NCC) cohort was analyzed by immunohistochemical staining, and the relationship between HNRNPC expression and survival rate evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Several pathways that were significantly enriched in the HNRNPC high expression group were identified by Gene Set Enrichment Analysis (GSEA).ResultsFive data sets from the Oncomine and GEPIA databases all supported that HNRNPC expression is significantly higher in LUAD than in normal lung tissue. In TCGA cohort, HNRNPC was highly expressed in LUAD tissues and significantly related to age, sex, smoking history, ethnicity, lymph node metastasis, and TNM staging (P < 0.001). High HNRNPC expression was significantly correlated with poor prognosis in the three cohorts (NCC, TCGA, and K-M plotter) (P < 0.05). Multivariate Cox regression analysis showed that HNRNPC expression was an independent prognostic factor in both TCGA and NCC cohorts (P < 0.05). Further, 10 significantly enriched pathways were identified from TCGA data and 118 lung cancer cell lines in CCLE, respectively.ConclusionsHigh HNRNPC expression is significantly related to poor overall survival in patients with LUAD, suggesting that HNRNPC may be a cancer-promoting factor and a potential prognostic biomarker in LUAD.


2014 ◽  
Vol 42 (15) ◽  
pp. 9908-9924 ◽  
Author(s):  
Jen-Hao Yang ◽  
Yi-Ying Chiou ◽  
Shu-Ling Fu ◽  
I-Yun Shih ◽  
Tsai-Hsuan Weng ◽  
...  

Abstract Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA-binding protein involved in chromatin remodeling, RNA processing and the DNA damage response. In addition, increased hnRNPK expression has been associated with tumor development and progression. A variety of post-translational modifications of hnRNPK have been identified and shown to regulate hnRNPK function, including phosphorylation, ubiquitination, sumoylation and methylation. However, the functional significance of hnRNPK arginine methylation remains unclear. In the present study, we demonstrated that the methylation of two essential arginines, Arg296 and Arg299, on hnRNPK inhibited a nearby Ser302 phosphorylation that was mediated through the pro-apoptotic kinase PKCδ. Notably, the engineered U2OS cells carrying an Arg296/Arg299 methylation-defective hnRNPK mutant exhibited increased apoptosis upon DNA damage. While such elevated apoptosis can be diminished through addition with wild-type hnRNPK, we further demonstrated that this increased apoptosis occurred through both intrinsic and extrinsic pathways and was p53 independent, at least in part. Here, we provide the first evidence that the arginine methylation of hnRNPK negatively regulates cell apoptosis through PKCδ-mediated signaling during DNA damage, which is essential for the anti-apoptotic role of hnRNPK in apoptosis and the evasion of apoptosis in cancer cells.


2015 ◽  
Vol 12 (1) ◽  
pp. 14 ◽  
Author(s):  
Thanyaporn Dechtawewat ◽  
Pucharee Songprakhon ◽  
Thawornchai Limjindaporn ◽  
Chunya Puttikhunt ◽  
Watchara Kasinrerk ◽  
...  

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