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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
microRNAs target SRSF7 splicing factor to modulate the expression of osteopontin splice variants in renal cancer
Joanna Boguslawska1, Elzbieta Sokol1, Beata Rybicka1
1Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland.
Abstract:
SRSF7 is a SR splicing factor involved in the regulation of splicing and mRNA export of cancer-related genes. The mechanisms regulating the expression of SRSF7 are unknown. This study shows that SRSF7 expression in cancer cells is regulated by microRNAs: short, non-coding RNAs that bind to 3'UTR of target genes and downregulate their expression. We show that microRNAs miR-30a-5p and miR-181a-5p together with SRSF7 form regulatory feedback loop in which the expression of microRNAs is recurrently regulated by its target. Finally, we demonstrate that silencing of SRSF7 affects the expression of osteopontin splice variants and decreases proliferation rate of renal cancer cells.
Insights
SRSF7 gene expression in cancer is controlled by microRNAs (miRNAs). These miRNAs and SRSF7 form a feedback loop, impacting cancer cell proliferation and osteopontin splicing in renal cancer.
Area of Science:
- Molecular Biology
- Cancer Genetics
- RNA Biology
Background:
- SRSF7 (Serine/Arginine-rich Splicing Factor 7) is a key splicing factor regulating cancer-related genes.
- The regulatory mechanisms governing SRSF7 expression remain largely uncharacterized.
Purpose of the Study:
- To elucidate the regulatory mechanisms controlling SRSF7 expression in cancer cells.
- To investigate the functional impact of SRSF7 regulation on cancer cell behavior.
Main Methods:
- Analysis of microRNA (miRNA) regulation of SRSF7.
- Identification of specific miRNAs (miR-30a-5p and miR-181a-5p) targeting SRSF7.
- Experimental validation of a feedback loop between SRSF7 and target miRNAs.
- Assessment of SRSF7 silencing effects on osteopontin splicing and renal cancer cell proliferation.
Main Results:
- SRSF7 expression is directly regulated by specific microRNAs (miRNAs).
- A novel feedback loop exists where SRSF7 and miRNAs mutually regulate each other's expression.
- Silencing SRSF7 alters osteopontin splice variant expression and reduces renal cancer cell proliferation.
Conclusions:
- MicroRNAs, specifically miR-30a-5p and miR-181a-5p, play a critical role in regulating SRSF7 expression in cancer.
- The identified feedback loop represents a new regulatory mechanism in cancer biology.
- Targeting the SRSF7-miRNA axis may offer therapeutic strategies for renal cancer by affecting cell proliferation and alternative splicing.
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