Association of MHC class-III gene polymorphisms with ER-positive breast cancer in Chinese Han population

Pan, Qinghua; Ning, Yunye; Chen, L.Z.; Zhang, S.; Liu, Zhenzhen; Yang, Xu; Wei, Wen; Wei, Haitao; Li, Q.G.; Yue, Haiying; Wang, J.X.

doi:10.4238/2012.september.17.1

Cited by 13 publications

(10 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epidemiology studies demonstrated association between Prrc2a SNPs and the risk of cancer, 44,45 rheumatoid arthritis, 46 insulin-dependent diabetes mellitus (IDDM) 47 , and obesity. 48 However, the roles of Prrc2a in the nervous system remained unknown despite its high expression in the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

et al. 2018

View full text Add to dashboard Cite

While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

et al. 2018

View full text Add to dashboard Cite

show abstract

“… 4 PRRC2A has been defined as the increased risk of developing rheumatoid arthritis (RA), an auto-immune disease. 5 In addition, a single nucleotide polymorphism of PRRC2A was associated with ER-positive breast cancer, 6 lung cancer, 7 and non-Hodgkin lymphoma. 8 However, its expression profiles and molecular functions in HCC have not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

PRRC2A Promotes Hepatocellular Carcinoma Progression and Associates with Immune Infiltration

Liu¹,

Zhang²,

Wang³

et al. 2021

JHC

View full text Add to dashboard Cite

Purpose Hepatocellular carcinoma (HCC) has high morbidity and poor prognosis due to the propensity of recurrence and metastasis. Emerging studies have confirmed that proline-rich coiled-coil2A (PRRC2A) plays a crucial role in tumorigenesis and immunoregulation. However, its expression status and biological functions in HCC remain poorly documented. Methods The presence and prognostic value of PRRC2A were determined by a tissue microarray (TMA) cohort and multiple databases, mainly from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC). Functional enrichment analysis was applied to identify the mechanisms of PRRC2A in HCC. The biological function of PRRC2A in HCC progression in vitro was determined by CCK-8, colony formation, EdU, transwell migration and invasion assays. Moreover, the Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithms, immunophenoscore (IPS) and public available immunotherapy cohorts were performed to classify their associations with tumor-infiltrating immune cells and immunotherapy. Results PRRC2A was upregulated in HCC at both mRNA and protein levels. High PRRC2A expression was correlated with poor prognosis and could be an independent risk factor. Functional enrichment analysis demonstrated that elevated PRRC2A was significantly correlated with the activation of various oncogenic pathways. Additionally, in vitro experiments confirmed that silencing PRRC2A could suppress the proliferation and metastasis capacities of HCC cells. More importantly, PRRC2A was negatively associated with many anti-tumor immune cells, but positively related to the expression of markers of exhaustive T cells. And HCC patients with high PRRC2A were more likely to be nonresponsive to immunotherapy. Conclusion This study explored the predictive value and biological roles of PRRC2A in HCC progression and indicated that it might be a potential biomarker for HCC patients and a predictor for immunotherapy.

show abstract

“…PRRC2A is highly expressed in the hypothalamus, 30 which is involved with regulation of most endocrine organs, and mainly affects hypothalamic-pituitary-adrenal and hypothalamic-pituitarygonadal axes. 31 In addition, this gene has been reported to be associated with the age at menopause, 32 ER-and PR-positive breast cancer, 33 and type 1 diabetes mellitus, 34 indicating a role for PRRC2A in sex hormone regulation and immune inflammation. A predominance in women and a low risk of SLE development in prepubertal or postmenopausal women also suggest a role for estrogen in disease predisposition.…”

Section: Discussionmentioning

confidence: 99%

Association Analysis of the MHC in Lupus Nephritis

Liu

et al. 2017

JASN

View full text Add to dashboard Cite

Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including amino acid 11 (<0.001), amino acid 45 (<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), amino acid 156 (<0.001), amino acid 76 (<0.001), and a missense variant in (rs114580964;<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

show abstract

Association of MHC class-III gene polymorphisms with ER-positive breast cancer in Chinese Han population

Cited by 13 publications

References 26 publications

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

PRRC2A Promotes Hepatocellular Carcinoma Progression and Associates with Immune Infiltration

Association Analysis of the MHC in Lupus Nephritis

Contact Info

Product

Resources

About