Although aberrant splicing events of genes are closely related to the development and progression of colorectal cancer (CRC), the mapping of abnormal splicing events, especially alternative splicing (AS) event types and the underlying effects, remain investigational. In the present study, we analyzed a public RNA-seq database (GSE138202) and identified 14,314 significant AS events in CRC patients compared to healthy individuals. Most of the key genes such as oncogenes involved in the development of CRC have different AS event types. Moreover, the results demonstrate that certain AS events may play a significant role in the functioning of key genes involved in splicing factors and microRNAs. Furthermore, we observed that the oncogene CDK4 in CRC tends to undergo exon 2 skipping AS events, resulting in a stronger tendency for protein expression to form complexes with CCND1, thereby inhibiting the cell cycle and weakening cell proliferation, while enhancing cell migration capability. These findings not only provide new insights into the mechanism of AS in regulating CRC, but also offers a theoretical basis for targeted splicing therapy in CRC.
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http://dx.doi.org/10.1007/s12672-024-01149-z | DOI Listing |
NPJ Precis Oncol
January 2025
Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University School of Medicine, Durham, NC, 27710, USA.
Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.
View Article and Find Full Text PDFEpilepsia
January 2025
Applied Translational Neurogenomics Group, Vlaams Instituut voor Biotechnology (VIB) Center for Molecular Neurology, VIB, Antwerp, Belgium.
Objective: This study aims to improve genetic diagnosis in childhood onset epilepsy with neurodevelopmental problems by utilizing RNA sequencing of fibroblasts to identify pathogenic variants that may be missed by exome sequencing and copy number variation analysis.
Methods: We enrolled 41 individuals with childhood onset epilepsy and neurodevelopmental problems who previously had inconclusive genetic testing. Fibroblast samples were cultured and analyzed using RNA sequencing to detect aberrant expression, aberrant splicing, and monoallelic expression using the Detection of RNA Outlier Pipeline (DROP) pipeline.
Cell Signal
January 2025
Jinhua Advanced Research Institute, Jinhua 321019, China. Electronic address:
Vascular calcification(VC) significantly increases the risk of cardiovascular events, leading to thickening of the myocardium and arteries, coronary heart disease, heart failure, and potentially triggering myocardial infarction and sudden cardiac death. Although VC is a reversible process, there are currently no methods or medications in clinical practice that can completely reverse or cure it. The current treatment strategies primarily focus on slowing the progression of VC and exploring new diagnostic and therapeutic approaches, making the identification of early diagnostic markers for VC particularly important.
View Article and Find Full Text PDFLife Med
April 2024
Collaborative Innovation Center of Genetics and Development, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai 200438, China.
As the most prevalent type of alternative splicing in animal cells, exon skipping plays an important role in expanding the diversity of transcriptome and proteome, thereby participating in the regulation of diverse physiological and pathological processes such as development, aging, and cancer. Cellular senescence serving as an anti-cancer mechanism could also contribute to individual aging. Although the dynamic changes of exon skipping during cellular senescence were revealed, its biological consequence and upstream regulator remain poorly understood.
View Article and Find Full Text PDFFront Physiol
January 2025
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
A transport protein's turnover rate (TOR) is the maximum rate of substrate translocation under saturating conditions. This parameter represents the number of transporting events per transporter molecule (assuming a single transport site) per second (s). From this standpoint, a transporter's TOR is similar to an enzyme's catalytic constant.
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