hnrnpa0

Alternative splicing (AS) plays an important role in various physiological processes in eukaryotes, such as the stress response. However, patterns of AS events remain largely unexplored during salinity acclimation in fishes. In this study, we conducted AS analysis using RNA-seq datasets to explore splicing patterns in the gill tissues of rainbow trout exposed to altered salinity environments, ranging from 0 ‰ (T0) to 30 ‰ (T30). The results revealed 1441, 351, 483, 1051 and 1049 differentially alternatively spliced (DAS) events in 5 pairwise comparisons, including T6 vs...

Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously...

Adult T-cell leukemia/lymphoma (ATLL) is pathogen-caused cancer that is progressed after the infection by human T-cell leukemia virus type 1. Four significant subtypes comprising acute, lymphoma, chronic, and smoldering have been identified for this cancer. However, there are no trustworthy prognostic biomarkers for these subtypes. We utilized a combination of two powerful network-based and machine-learning algorithms including differential co-expressed genes (DiffCoEx) and support vector machine-recursive feature elimination with cross-validation (SVM-RFECV) methods to categorize disparate ATLL subtypes from asymptomatic carriers (ACs)...

P53 inactivation occurs in about 50% of human cancers, where p53-driven p21 activity is devoid and p27 becomes essential for the establishment of the G1/S checkpoint upon DNA damage. Here, this work shows that the E2F1-responsive lncRNA LIMp27 selectively represses p27 expression and contributes to proliferation, tumorigenicity, and treatment resistance in p53-defective colon adenocarcinoma (COAD) cells. LIMp27 competes with p27 mRNA for binding to cytoplasmically localized hnRNA0, which otherwise stabilizes p27 mRNA leading to cell cycle arrest at the G0/G1 phase...

Myelodysplastic syndromes (MDS) are considered to be diseases associated with splicing defects. A large number of genes involved in the pre-messenger RNA splicing process are mutated in MDS. Deletion of 5q and 7q are of diagnostic value, and those chromosome regions bear the numbers of splicing genes potentially deleted in del(5q) and del(7q)/-7 MDS. In this review, we present the splicing genes already known or suspected to be implicated in MDS pathogenesis. First, we focus on the splicing genes located on chromosome 5 ( HNRNPA0 , RBM27 , RBM22 , SLU7 , DDX41 ), chromosome 7 ( LUC7L2 ), and on the SF3B1 gene since both chromosome aberrations and the SF3B1 mutation are the only genetic abnormalities in splicing genes with clear diagnostic values...

miR-486 is a myogenic microRNA, and its reduced skeletal muscle expression is observed in muscular dystrophy. Transgenic overexpression of miR-486 using muscle creatine kinase promoter (MCK-miR-486) partially rescues muscular dystrophy phenotype. We had previously demonstrated reduced circulating and skeletal muscle miR-486 levels with accompanying skeletal muscle defects in mammary tumor models. To determine whether skeletal muscle miR-486 is functionally similar in dystrophies and cancer, we performed functional limitations and biochemical studies of skeletal muscles of MMTV-Neu mice that mimic HER2+ breast cancer and MMTV-PyMT mice that mimic luminal subtype B breast cancer and these mice crossed to MCK-miR-486 mice...

(Genome-wide Association Studies) GWAS have identified ∼42 late-onset Alzheimer's disease (LOAD)-associated loci, each of which contains multiple single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) and most of these SNPs are in the non-coding region of human genome. However, how these SNPs regulate risk gene expression remains unknown. In this work, by using a set of novel techniques, we identified 6 functional SNPs (fSNPs) rs9271198, rs9271200, rs9281945, rs9271243, and rs9271247 on the LOAD-associated HLA-DRB1/DQA1 locus and 42 proteins specifically binding to five of these 6 fSNPs...

Esophageal carcinoma (ESCA) affects 4,450,000 people and causes approximately 400,000 deaths annually worldwide, making it the sixth most lethal and eighth most common cancer. Patients with ESCA are often diagnosed at the later stages, in which cancer cell metastasis is the main factor contributing to the low 5-year survival rate (less than 20%) of this disease. Long non-coding RNAs (lncRNAs) are a group of regulatory RNAs with a length of >200 nucleotides but which fail to encode proteins. In this study, by using real-time quantitative PCR (qPCR), we found that the expression of the miR205 host gene (miR205HG; a lncRNA) was downregulated in ESCA tumors when compared with normal esophageal tissues or adjacent normal tissues of tumors...

Background: Abnormal epigenetic alterations can contribute to the development of human malignancies. Identification of these alterations for early screening and prognosis of clear cell renal cell carcinoma (ccRCC) has been a highly sought-after goal. Bioinformatic analysis of DNA methylation data provides broad prospects for discovery of epigenetic biomarkers. However, there is short of exploration of methylation-driven genes of ccRCC. Methods: Gene expression data and DNA methylation data in metastatic ccRCC were sourced from the Gene Expression Omnibus (GEO) database...

Endometrial cancer remains the most common malignancy of the female genital system in developed countries. Tumor suppressor genes are responsible for controlling the cells fate in the cell cycle and preventing cancerogenesis. Gene expression affects cancer progression and is modulated by microRNAs defined as both tumor suppressors and oncogenes. These molecules indirectly regulate multiple processes like cell proliferation, differentiation and apoptosis. The aim of this study was to analyze miRNAs expression that can regulate the activity of tumor suppressor genes related to the cell cycle in patients with endometrioid endometrial cancer...

Genome-wide approaches applied for the identification of new hereditary colorectal cancer (CRC) genes, identified several potential causal genes, including RPS20, IL12RB1, LIMK2, POLE2, MRE11, POT1, FAN1, WIF1, HNRNPA0, SEMA4A, FOCAD, PTPN12, LRP6, POLQ, BLM, MCM9, and the epigenetic inactivation of PTPRJ. Here we attempted to validate the association between variants in these genes and nonpolyposis CRC by performing a mutational screening of the genes and PTPRJ promoter methylation analysis in 473 familial/early-onset CRC cases, a systematic review of the published cases, and assessment of allele frequencies in control population...

RNA regulation mediating RNA-binding proteins (RBPs) have been shown to be related to the maintenance of homeostasis as well as cancer progression. However, the tumor-associated functions as well as the detailed mechanisms underlying the anti-tumor effects of most RBPs have yet to be explored. We herein report that the phosphorylated heterogeneous ribonucleoprotein (hnRNP) A0 promotes mitosis through the RAS-associated protein 3 GTPase-activating protein catalytic subunit 1 (RAB3GAP1)-Zeste white 10 interactor (ZWINT1) cascade...

Background: To investigate the expression of S1 RNA binding domain 1 (SRBD1) in non-small cell lung cancer tissue and the effects of SRBD1 silencing on the biological behaviors of human non-small cell lung cancer cells, and to explore the molecular mechanism of SRBD1functions in human non-small cell lung cancer cells. Methods: Expressions of SRBD1 in human non-small cell lung cancer tissues and cell lines were examined by immunostaining and RT-PCR. shRNAs of SRBD1 were chemically synthesized and transfected into A549 and NCI-H1299 cells by lentivirus...

Alternative splicing (AS) constitutes a major reason for messenger RNA (mRNA) and protein diversity. Increasing studies have shown a link to splicing dysfunction associated with malignant neoplasia. Systematic analysis of AS events in kidney cancer remains poorly reported. Therefore, we generated AS profiles in 533 kidney renal clear cell carcinoma (KIRC) patients in The Cancer Genome Atlas (TCGA) database using RNA-seq data. Then, prognostic models were developed in a primary cohort (N = 351) and validated in a validation cohort (N = 182)...

Dysregulation of splicing factor expression is emerging as a driver of human ageing; levels of transcripts encoding splicing regulators have previously been implicated in ageing and cellular senescence both in vitro and in vivo. We measured the expression levels of an a priori panel of 20 age- or senescence-associated splicing factors by qRT-PCR in peripheral blood samples from the InCHIANTI Study of Aging, and assessed longitudinal relationships with human ageing phenotypes (cognitive decline and physical ability) using multivariate linear regression...

Most of our knowledge about translation regulatory mechanisms comes from studies on lower organisms. However, the translation control system of higher organisms is less understood. Here we find that in 5' untranslated region (5'UTR) of human Annexin II receptor (AXIIR) mRNA, there are two upstream open reading frames (uORFs) acting in a fail-safe manner to inhibit the translation from the main AUG. These uORFs are unfavorable for re-initiation after termination of uORF translation. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), hnRNPA0 and ELAV like RNA binding protein 1 (ELAVL1) bind to the 5'UTR of AXIIR mRNA...

PURPOSE: Endometrial cancer is the most common gynecological malignancy in developed countries. The role of tumor suppressor genes (TSG) in endometrioid endometrial adenocarcinoma (EEC) has an important impact on patient survival prognosis. Thus, it is important to identify TSG transcripts that differentiate endometrial adenocarcinoma into various pathomorphological grades. The aim of this study was to analyze the expression profile of tumor suppressor genes related to the cell cycle in patients with endometrial adenocarcinoma across histological differentiation and to identify transcripts which differentiate endometrium into various pathomorphological grades...

In normal cells, p53 is activated by DNA damage checkpoint kinases to simultaneously control the G1/S and G2/M cell cycle checkpoints through transcriptional induction of p21(cip1) and Gadd45α. In p53-mutant tumors, cell cycle checkpoints are rewired, leading to dependency on the p38/MK2 pathway to survive DNA-damaging chemotherapy. Here we show that the RNA binding protein hnRNPA0 is the "successor" to p53 for checkpoint control. Like p53, hnRNPA0 is activated by a checkpoint kinase (MK2) and simultaneously controls both cell cycle checkpoints through distinct target mRNAs, but unlike p53, this is through the post-transcriptional stabilization of p27(Kip1) and Gadd45α mRNAs...

The MK2/hnRNPA0 promotes the chemoresistance of TP53-deficient NSCLC tumors.

No abstract text is available yet for this article.