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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
Alterations of mRNA splicing in primary effusion lymphomas
Zongdong Li1, Langxing Pan, Ethel Cesarman
1Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Abstract:
Primary effusion lymphoma (PEL) is a unique form of malignant lymphoma associated with infection by the Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8). The majority of PELs also contain the EBV genome. Although viral infection is believed to play a critical role in the pathogenesis of PEL, it has been suggested that additional molecular lesions are required for the development of PEL. Alternative splicing of pre-mRNA is an important mechanism in the regulation of cellular and viral gene expression. Deregulation of pre-mRNA splicing may shift the gene expression balance and lead to the development of cancer. In order to investigate mRNA splicing in PELs, we examined mRNA splicing of three genes, DNA polymerase beta (pol beta), Bcl-x and CD45, in eight PEL cell lines. We found that the average variant percentage of pol beta in PEL cell lines is two times higher than in peripheral blood mononuclear cells (PBMC) and that the variant pattern of genes bcl-x and CD45 is quite different in PEL cell lines than in PBMC. In addition, we also found that the percentage of variant pol beta increased two-fold in PBMC following Epstein-Barr virus (EBV) infection. Therefore, viral infection may contribute to mRNA alternative splicing in PEL. In order to explore the mechanism by which viral infection affects mRNA splicing, we also examined the roles of genes KS-SM, SM and EBERs and viral copies in mRNA splicing. Our findings indicate that various factors acting as positive or negative regulators may be involved in mRNA alternative splicing caused by viral infection. In conclusion, mRNA splicing in PEL can be altered by viral infection and this alteration may contribute to the pathogenesis of PEL.
Insights
Primary effusion lymphoma (PEL), a cancer linked to KSHV/HHV-8, shows altered mRNA splicing. Viral infections like EBV may drive these splicing changes, potentially contributing to PEL development.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Primary effusion lymphoma (PEL) is a distinct malignancy associated with KSHV/HHV-8 and often EBV.
- While viral infection is crucial, additional molecular events are likely necessary for PEL development.
- Alternative splicing of pre-mRNA regulates gene expression and its deregulation can lead to cancer.
Purpose of the Study:
- To investigate mRNA alternative splicing patterns in PEL.
- To determine if viral infections influence mRNA splicing in PEL.
- To explore the mechanisms by which viruses affect mRNA splicing.
Main Methods:
- Examined mRNA splicing of DNA polymerase beta (pol beta), Bcl-x, and CD45 in eight PEL cell lines.
- Compared splicing patterns in PEL cell lines with peripheral blood mononuclear cells (PBMC).
- Investigated the effect of Epstein-Barr virus (EBV) infection on PBMC splicing and analyzed viral factors (KS-SM, SM, EBERs) in PEL splicing.
Main Results:
- PEL cell lines exhibited a two-fold higher variant percentage of pol beta compared to PBMC.
- Distinct splicing patterns for Bcl-x and CD45 were observed in PEL cell lines versus PBMC.
- EBV infection increased pol beta variant percentage in PBMC, suggesting viruses can alter splicing.
Conclusions:
- mRNA splicing is altered in PEL and can be influenced by viral infection.
- These viral-induced splicing alterations may play a role in the pathogenesis of PEL.
- Multiple regulatory factors likely mediate virus-induced mRNA alternative splicing.
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