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Updated: Jun 14, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
SRSF3 suppresses RCC tumorigenesis and progression via regulating SP4 alternative splicing
Liuxu Zhang1, Hongning Zhang2, Yuangui Tang1
1Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Laboratory for Clinical Medicine, Capital Medical University, Beijing 100069, China.
None:
Abnormal alternative splicing (AS) caused by dysregulated expression of splicing factors plays a crucial role in tumorigenesis and progression. The serine/arginine-rich (SR) RNA-binding protein family is a major class of splicing factors regulating AS. However, their roles and mechanisms in renal cell carcinoma (RCC) development and progression are not fully understood. Here, we found that SR splicing factor 3 (SRSF3) was an important splicing factor affecting RCC progression. SRSF3 was downregulated in RCC tissues and its low level was associated with decreased overall survival time of RCC patients. SRSF3 overexpression suppressed RCC cell malignancy. Mechanistically, the binding of SRSF3 to SP4 exon 3 led to the inclusion of SP4 exon 3 and the increase of long SP4 isoform (L-SP4) level in RCC cells. L-SP4, but not S-SP4 overexpression suppressed RCC cell malignancy. Meanwhile, L-SP4 participated in SRSF3-mediated anti-proliferation by transcriptionally promoting SMAD4 expression. Taken together, our findings provide new insights into the anticancer mechanism of SRSF3, suggesting that SRSF3 may serve as a novel potential therapeutic target for RCC.
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