Background: Tumor-specific isoforms generated by alternative splicing (AS) are demonstrated to contribute to tumor progression and can represent potential biomarkers. NOVA2 is an AS factor that in physiological conditions regulates endothelial cells' (ECs) polarity and vessel lumen maturation, likely by mediating AS of apical-basal polarity regulators. However, NOVA2 expression in tumor ECs and its regulation have never been investigated.
Methods: To elucidate this, 40 colorectal cancer patients were enrolled and NOVA2 expression was investigated by immunohistochemistry in samples bearing both the normal mucosa and the tumor tissue.
Results: NOVA2 was found expressed in ECs of tumor vasculature and, importantly, it was upregulated in tumor ECs with respect to normal mucosa ECs in all cases (<0.001). The same samples analyzed by immunohistochemistry for the expression HIF1α, a marker of hypoxia, showed a positive and significant association with NOVA2 levels (=0.045). Of note, NOVA2 was upregulated by hypoxia also in an in vitro ECs model.
Conclusion: Our results provide, for the first time, evidence of NOVA2 expression and upregulation in tumor ECs and highlight hypoxia as a potential regulatory factor. These findings open a completely new perspective to study tumor vasculature and to uncover NOVA2 as a potential source of biomarkers and therapeutic targets based on AS isoforms.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157992 | PMC |
| http://dx.doi.org/10.2147/OTT.S171678 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cellular Uptake of Tau Aggregates Triggers Disulfide Bond Formation in Four-Repeat Tau Monomers.
ACS Chem Neurosci
December 2024
Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80208, United States.
Oxidative stress is an important driver of aging and has been linked to numerous neurodegenerative disorders, including Alzheimer's disease. A key pathological hallmark of Alzheimer's are filamentous inclusions made of the microtubule associated protein Tau. Based on alternative splicing, Tau protein can feature either three or four microtubule binding repeats.
View Article and Find Full Text PDFUnlabelled: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies.
View Article and Find Full Text PDFRNA-binding protein quaking: a multifunctional regulator in tumour progression.
Ann Med
December 2025
Department of Breast Surgery, Second Affiliated Hospital and Cancer Institute (Provincial Key Laboratory of Tumor Microenvironment and Immunotherapy, Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education), Zhejiang University School of Medicine, Hangzhou, China.
Background: Quaking (QKI) is a member of the signal transduction and activators of RNA (STAR) family, performing a crucial multifunctional regulatory role in alternative splicing, mRNA precursor processing, mRNA transport and localization, mRNA stabilization, and translation during tumour progression. Abnormal QKI expression or fusion mutations lead to aberrant RNA and protein expression, thereby promoting tumour progression. However, in many types of tumour, QKI played a role as tumour suppressor, the regulatory role of QKI in tumour progression remains ambiguous.
View Article and Find Full Text PDFInterrogation of RNA-bound proteome with XRNAX illuminates molecular alterations in the mouse brain affected with dysmyelination.
Cell Rep
December 2024
Department of Non-coding RNAs, Institute of Bioorganic Chemistry of the Polish Academy of Sciences, 61-704 Poznan, Poland. Electronic address:
RNA-protein interactions orchestrate hundreds of pathways in homeostatic and stressed cells. We applied an RNA-protein interactome capture method called protein cross-linked RNA extraction (XRNAX) to shed light on the RNA-bound proteome in dysmyelination. We found sets of canonical RNA-binding proteins (RBPs) regulating alternative splicing and engaged in the cytoplasmic granules to be perturbed at the level of their RNA interactome.
View Article and Find Full Text PDFPost-transcriptional regulation of behavior plasticity in social insects.
Curr Opin Insect Sci
December 2024
Department of Entomology, College of Plant Protection, China Agricultural University, Beijing, China. Electronic address:
Social insects often show remarkable behavioral plasticity, which is closely associated with their respective castes. The underpinnings of this plasticity are complex, involving genetic differences among individuals within a colony and regulation of gene expression at multiple levels. Post-transcriptional regulation, which increases the complexity of the transcriptome, plays a crucial role in the multilayer regulatory network that influences social insect behavior.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!