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Published on: January 7, 2019
Pan-cancer oncogenic properties and therapeutic potential of SF3B4
Yanmei Shi1, Qimei Pan1, Wenli Chen2
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, PR China.
Abstract:
Splicing factor 3B (SF3B) subunit 4 (SF3B4), an SF3B complex component essential for spliceosome assembly and accurate splicing, plays a major role in cancer development. However, the precise mechanism through which SF3B4 contributes to tumor growth remains unclear. Here, we demonstrate that SF3B4 is strongly expressed in patients with various cancer types and correlated with their survival. By using hepatocellular carcinoma (HCC) as a model, we reveal that SF3B4's interactions with and regulatory influence on the checkpoint protein BUB1 are essential for appropriate cancer cell mitosis and proliferation. Our results thus demonstrate the roles of SF3B4 as both a cell-cycle regulator and an oncogenic factor in HCC, highlighting its potential as a pan-cancer therapeutic target and diagnostic biomarker.
Insights
Splicing factor 3B subunit 4 (SF3B4) is highly expressed in cancers and drives tumor growth by regulating mitosis. Targeting SF3B4 may offer a new strategy for cancer therapy and diagnosis.
Area of Science:
- Molecular biology
- Cancer research
- Cell biology
Background:
- Splicing factor 3B (SF3B) subunit 4 (SF3B4) is crucial for spliceosome function.
- SF3B4's role in oncogenesis is not fully understood.
- Understanding SF3B4's mechanism in cancer is vital for therapeutic development.
Purpose of the Study:
- To investigate the role of SF3B4 in various cancer types.
- To elucidate the mechanism by which SF3B4 promotes tumor growth, using hepatocellular carcinoma (HCC) as a model.
- To evaluate SF3B4 as a potential pan-cancer therapeutic target and diagnostic biomarker.
Main Methods:
- Analysis of SF3B4 expression in patient cancer samples.
- Correlation of SF3B4 expression with patient survival data.
- Investigation of SF3B4's interaction with BUB1 in HCC cells.
- Assessment of SF3B4's impact on mitosis and proliferation in HCC.
Main Results:
- SF3B4 is highly expressed across diverse cancer types and correlates with poor patient survival.
- SF3B4 interacts with and regulates the checkpoint protein BUB1.
- SF3B4 is essential for accurate mitosis and proliferation of cancer cells, particularly in HCC.
- SF3B4 functions as a cell-cycle regulator and oncogenic factor in HCC.
Conclusions:
- SF3B4 is a significant oncogenic factor in various cancers, including HCC.
- SF3B4's interaction with BUB1 is critical for cancer cell division and proliferation.
- SF3B4 presents a promising target for pan-cancer therapeutics and a potential diagnostic biomarker.
