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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Ribosomal protein L8 regulates the expression and splicing pattern of genes associated with cancer-related pathways
Leilei Xu1, Gui Yang1, Bin Song2
1Department of Bone Tumor, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, P.R. China.
Background/Aim:
Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown.
Materials And Methods:
RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay.
Results:
RPL8-OE inhibited cell proliferation and promoted cell apoptosis. RPL8 regulated the differential expression of many oncogenic genes and the occurrence of RASEs. Many DEGs and RASE genes (RASGs) were enriched in tumorigenesis and tumor progression-related pathways, including angiogenesis, inflammation, and regulation of cell proliferation. RPL8 could regulate the RASGs enriched in the negative regulation of apoptosis, consistent with its proapoptosis function. Furthermore, RPL8 may influence cancer-related DEGs by modulating the alternative splicing of transcription factors.
Conclusion:
RPL8 might affect the phenotypes of cancer cells by altering the transcriptome profiles, including gene expression and splicing, which provides novel insights into the biological functions of RPL8 in tumor development.
Insights
Ribosomal protein L8 (RPL8) overexpression inhibits cancer cell proliferation and promotes apoptosis by altering gene expression and alternative splicing. This study reveals novel insights into RPL8's role in tumor development.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Ribosomal proteins have extraribosomal functions, including roles in apoptosis and oncogenesis.
- Ribosomal protein L8 (RPL8) is implicated in tumor development, but its specific functions and pathways remain unclear.
Purpose of the Study:
- To investigate the biological functions and pathways of RPL8 in cancer.
- To analyze the effects of RPL8 overexpression on cell proliferation, apoptosis, gene expression, and alternative splicing.
Main Methods:
- Overexpression of RPL8 (RPL8-OE) in HeLa cells.
- MTT assay for cell proliferation and flow cytometry for apoptosis.
- Transcriptome sequencing to identify differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs), validated by RT-qPCR.
Main Results:
- RPL8-OE inhibited cell proliferation and promoted apoptosis.
- RPL8 regulated DEGs and RASEs involved in tumorigenesis, angiogenesis, inflammation, and cell proliferation.
- RPL8 influenced genes related to apoptosis regulation and potentially modulated transcription factors via alternative splicing.
Conclusions:
- RPL8 affects cancer cell phenotypes by altering transcriptome profiles, including gene expression and splicing.
- These findings offer new perspectives on the biological functions of RPL8 in tumor development.
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