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Updated: Aug 29, 2025
Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of
Jia-Fu Feng1,2, Wen-Yu Yang3, Yao-Dong Wang1,4
1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.
Background:
Covalently closed circular RNAs (circRNAs) play critical oncogenic or anticancer roles in various cancers including renal cell carcinoma (RCC), pointing to their regulation as a promising strategy against development of RCC. We, thus, studied the tumor-suppressive role of circ_000829 in RCC through in vitro and in vivo experiments.
Methods:
The expression of circ_000829 was validated in clinical RCC tissues and RCC cell lines. Based on ectopic expression and knockdown experiments, we examined the interactions among circ_000829, serine and arginine rich splicing factor 1 (SRSF1), and solute carrier family 39 member 14 (SLC39A14, zinc transporter). Then, the effects of circ_000829, SRSF1, and SLC39A14 on cell cycle distribution and proliferation in vitro and on tumor growth in vivo were evaluated in RCC cells.
Results:
Circ_000829 was poorly expressed in RCC tissues and cells, while SRSF1 was highly expressed. Restoration of circ_000829 reduced the levels of SRSF1 and SLC39A14B, thereby repressing the RCC cell proliferation in vitro and tumor growth in vivo. Meanwhile, overexpression of SRSF1 and SLC39A14B promoted the proliferation and cell cycle entry of RCC cells. Mechanistically, circ_000829 directly bound to SRSF1, and SRSF1 enhanced the expression of SLC39A14B by mediating the alternative splicing of SLC39A14. SLC39A14B upregulation negated the effect of SLC39A14 knockdown on RCC cell proliferation.
Conclusion:
Hence, this study suggests the antiproliferative role of circ_000829 in RCC growth and further elucidates the underlying mechanism involving the inhibited SRSF1-mediated alternative splicing of SLC39A14 mRNA.
Insights
Circ_000829 acts as a tumor suppressor in renal cell carcinoma (RCC). It inhibits cancer growth by reducing SRSF1 and SLC39A14B levels, offering a potential therapeutic strategy for RCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Covalently closed circular RNAs (circRNAs) exhibit dual roles in cancer, impacting renal cell carcinoma (RCC) development.
- Understanding circRNA regulation is crucial for developing novel RCC therapeutic strategies.
Purpose of the Study:
- To investigate the tumor-suppressive function of circ_000829 in renal cell carcinoma (RCC).
- To elucidate the molecular mechanism underlying circ_000829's role in RCC progression.
Main Methods:
- Validated circ_000829 expression in clinical RCC tissues and cell lines.
- Conducted in vitro and in vivo experiments involving ectopic expression and knockdown of circ_000829, SRSF1, and SLC39A14.
- Assessed the impact on cell cycle, proliferation, and tumor growth.
Main Results:
- Circ_000829 was underexpressed in RCC, while SRSF1 was overexpressed.
- Restoring circ_000829 suppressed RCC proliferation and tumor growth by reducing SRSF1 and SLC39A14B.
- Circ_000829 directly binds SRSF1, inhibiting SRSF1-mediated alternative splicing of SLC39A14 mRNA.
Conclusions:
- Circ_000829 possesses an antiproliferative role in RCC.
- The mechanism involves inhibiting SRSF1-mediated alternative splicing of SLC39A14 mRNA, highlighting circ_000829 as a potential therapeutic target for RCC.
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