Related Experiment Video
Updated: Sep 4, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
The splicing factor SF3B4 drives proliferation and invasion in cervical cancer by regulating SPAG5
Yingwei Li1,2, Yuchao Diao3,4, Zixiang Wang3
1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China. sduliyingwei@126.com.
Abstract:
Regulation of alternative splicing (AS) by the splicing factor 3b (SF3B) family plays an essential role in cancer. However, the biological function of SF3B family members in cervical cancer (CC) needs to be further elucidated. In this study, we found that splicing factor 3b subunit 4 (SF3B4) was highly expressed in CC by bioinformatics analysis using cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) data from The Cancer Genome Atlas (TCGA). Then, we demonstrated that high expression of SF3B4 promoted proliferation and invasion abilities of CC cells in vitro and in vivo and that reduced expression of SF3B4 performed the opposite effect. Further RNA-seq and AS analysis showed that sperm-associated antigen 5 (SPAG5) was a downstream target gene of SF3B4. Interestingly, SPAG5 expression was decreased after SF3B4 knockdown because of retained introns (RIs) and reduced maturation of SPAG5 pre-mRNA. Importantly, SPAG5 deficiency impaired the oncogenic effects of SF3B4 overexpression on CC cells. In conclusion, SF3B4 promotes CC progression by regulating the effective splicing of SPAG5. SF3B4 could be a promising target for CC.
Insights
Splicing factor 3b subunit 4 (SF3B4) promotes cervical cancer (CC) progression by affecting sperm-associated antigen 5 (SPAG5) splicing. SF3B4 may be a potential therapeutic target for cervical cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Alternative splicing (AS) regulation by the splicing factor 3b (SF3B) family is crucial in cancer.
- The specific role of SF3B family members in cervical cancer (CC) requires further investigation.
Purpose of the Study:
- To elucidate the biological function of SF3B4 in cervical cancer.
- To identify downstream targets and mechanisms of SF3B4 in CC progression.
Main Methods:
- Bioinformatics analysis of The Cancer Genome Atlas (TCGA) CESC data.
- In vitro and in vivo experiments assessing cell proliferation and invasion.
- RNA sequencing (RNA-seq) and alternative splicing analysis.
Main Results:
- SF3B4 was highly expressed in CC and promoted CC cell proliferation and invasion.
- SF3B4 regulated the effective splicing of its downstream target, sperm-associated antigen 5 (SPAG5), leading to reduced SPAG5 maturation.
- SPAG5 deficiency counteracted the oncogenic effects of SF3B4 overexpression in CC cells.
Conclusions:
- SF3B4 promotes cervical cancer progression through the regulation of SPAG5 splicing.
- SF3B4 represents a potential therapeutic target for cervical cancer.
Related Concept Videos
RNA Splicing
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Cancer Cell Migration through Invadopodia
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Induced Pluripotent Stem Cells
Somatic...
Pre-mRNA Processing: RNA Splicing

