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SRrp35 suppresses cell proliferation and malignancy in hepatocellular carcinoma
Yandong Li1,2, Yun Lin1, Qun Li1
1Department of Oncology, Shanghai, China.
Aim:
Serine/arginine-rich (SR) proteins are known to be involved in alternative pre-mRNA splicing, RNA metabolism and cancer development. SRrp35 is a member of this family that antagonizes classical SR proteins in the regulation of splicing. However, the function of SRRP35 in cancer remains unclear to date. This study aims to investigate SRrp35 function in hepatocellular carcinoma (HCC).
Methods:
SRrp35 expression was accessed by quantitative real-time polymerase chain reaction in 32 pairs of clinical HCC samples and 12 kinds of HCC cell lines. The biological roles of Srrp35 were analyzed using cell viability, colony formation and soft agar growth assays in vitro and tumorigenicity in nude mice model.
Results:
SRrp35 was frequently downregulated in 62.5% (20/32) of HCC specimens and most of HCC cell lines. Enhanced expression of SRrp35 significantly suppressed cell proliferation and colony formation in an anchor-dependent and -independent manner, whereas knockdown of SRrp35 by RNA inference resulted in the opposite effects. In vivo, SRrp35 plays a suppressive role in developing tumor xenografts in line with the function in vitro.
Conclusion:
Our findings suggest that SRrp35 suppresses cell proliferation and malignancy in HCC and could be a potential therapeutic target for this disease.
Insights
Serine/arginine-rich protein 35 (SRrp35) suppresses hepatocellular carcinoma (HCC) cell growth and malignancy. Downregulation of SRrp35 is common in HCC, suggesting it is a potential therapeutic target for liver cancer.
Area of Science:
- Molecular biology
- Cancer research
- RNA splicing
Background:
- Serine/arginine-rich (SR) proteins regulate alternative pre-mRNA splicing, RNA metabolism, and cancer development.
- SRrp35 antagonizes classical SR proteins in splicing regulation, but its role in cancer is unclear.
Purpose of the Study:
- Investigate the function of SRrp35 in hepatocellular carcinoma (HCC).
Main Methods:
- Quantitative real-time PCR to assess SRrp35 expression in HCC samples and cell lines.
- In vitro assays (cell viability, colony formation, soft agar growth) and in vivo tumorigenicity assays in nude mice.
Main Results:
- SRrp35 was downregulated in 62.5% of HCC specimens and most HCC cell lines.
- Enhanced SRrp35 expression suppressed HCC cell proliferation and colony formation.
- SRrp35 knockdown promoted proliferation and colony formation; in vivo studies confirmed its tumor-suppressive role.
Conclusions:
- SRrp35 suppresses cell proliferation and malignancy in HCC.
- SRrp35 represents a potential therapeutic target for hepatocellular carcinoma.
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