Alternative splicing in tumor cells may be used as a molecular marker for the differential diagnosis of certain tumor types and assessment of prognosis. The aim of the present study was to investigate the associations among alternative splicing events, splicing factors, and the survival of patients with hepatocellular carcinoma (HCC). The alternative splicing event profiles of 371 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) SpliceSeq data, and the percent‑splice‑in value for each splicing event was calculated. The association between alternative splicing events and overall survival was evaluated. The most significant prognosis‑related splicing events were used to build up a prognostic index (PI). A total of 3,082 survival‑associated alternative splicing events were detected in HCC. The final PI based on all of the most significant candidate alternative splicing events exhibited better performance in distinguishing good or poor survival in patients compared to the PI based on a single type of splicing event. Receiver operating characteristic curves confirmed the high efficiency of the PI in predicting the survival of HCC patients, with an area under the curve of 0.914. The overexpression of 32 prognosis‑related splicing factor genes could also predict poor prognosis in patients with HCC. In conclusion, the constructed computational prognostic model based on HCC‑specific alternative splicing events may be used as a molecular marker for the prognosis of HCC.
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http://dx.doi.org/10.3892/ijo.2019.4834 | DOI Listing |
Nat Neurosci
January 2025
Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.
View Article and Find Full Text PDFNat Commun
January 2025
The National Engineering Laboratory of Crop Stress Resistance Breeding, School of Life Sciences, Anhui Agricultural University, Hefei, China.
Dissecting the mechanisms underlying heat tolerance is important for understanding how plants acclimate to heat stress. Here, we identify a heat-responsive gene in Arabidopsis thaliana, RNA-DIRECTED DNA METHYLATION 16 (RDM16), which encodes a pre-mRNA splicing factor. Knockout mutants of RDM16 are hypersensitive to heat stress, which is associated with impaired splicing of the mRNAs of 18 out of 20 HEAT SHOCK TRANSCRIPTION FACTOR (HSF) genes.
View Article and Find Full Text PDFCell Death Dis
January 2025
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438, Frankfurt, Germany.
The transcription factor p63 is expressed in many different isoforms as a result of differential promoter use and splicing. Some of these isoforms have very specific physiological functions in the development and maintenance of epithelial tissues and surveillance of genetic integrity in oocytes. The ASPP family of proteins is involved in modulating the transcriptional activity of the p53 protein family members, including p63.
View Article and Find Full Text PDFPhysiol Rep
January 2025
Department of Medicine, John A. Burns School of Medicine, University of Hawaii Mānoa, Honolulu, Hawaii, USA.
Inflammation and a metabolic shift from oxidative metabolism to glycolysis are common in the ischemic heart, the latter partly controlled by pyruvate kinase (muscle, PKM). We previously identified alternative splicing promoting the PKM2 isoform after myocardial infarction (MI). We examined the role of PKM2 physiological upregulation after MI, modeled by ligation of the left anterior descending coronary artery, using global PKM2 knockout (PKM2) mice.
View Article and Find Full Text PDFBMC Genomics
January 2025
The Key Lab for Biology of Crop Pathogens and Insect Pests and Their Ecological Regulation of Zhejiang Province, College of Advanced Agricultural Sciences, Zhejiang A&F University, Hangzhou, 311300, China.
Long non-coding RNA (lncRNA) plays important roles in animals and plants. In filamentous fungi, however, their biological function in infection stage has been poorly studied. Here, we investigated the landscape and regulation of lncRNA in the filamentous plant pathogenic fungus Botrytis cinerea by strand-specific RNA-seq of multiple infection stages.
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