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Shugoshin 1 expression in various cancers: a potential target for therapy
Indumathi Ankathatti Narayanaswamy1, Abhay Kumaraswamy Kattepur2, Kalyani Raju3
1Department of Cell Biology and Molecular Genetics, Sri Devaraj Urs Academy of Higher Education and Research (Deemed to be University), Kolar, Karnataka, 563 103, India.
Abstract:
Shugoshin 1 (SGO1) is one of the Shugoshin (guardian spirit) family proteins, which is reported to be majorly involved in the protection of centromeres and proper segregation of chromosomes during cell division. Recent studies found that the altered expression of SGO1 is associated with various cancers and genetic disorders, and suggested as a target for therapy. In the present study, we have reviewed the available literature on SGO1 gene and protein expression in various cancer-cell lines, animal models and cancer patients, and targeting SGO1 with siRNA/shRNA. A significant increase in the expression of SGO1 mRNA and protein levels were observed in prostate, renal, lung, breast, neuroblastoma, leukemia, hepatocellular, and colon cancer-cell lines and the levels were associated with increased cellular proliferation, invasion, and metastasis. The altered SGO1 levels were observed in SGO1 knockout/haploinsufficient mice compared to wild type and the levels were associated with increased chromosome instability and tumorigenesis. Consistent with cell lines, higher SGO1 expression was also observed in tumor tissues of cancer patients compared to adjacent normal tissue and the levels were positively correlated with tumor stage, grade, size, and hormonal status. Higher SGO1 expression was related to resistance to chemotherapeutic agents and the knockdown of SGO1 increased sensitivity to those agents. Furthermore, targeting SGO1 with siRNA/shRNA reduced the expression of SGO1 and proliferation, and induced apoptosis of cancer cells. Overall, the SGO1 expression levels were significantly higher in various cancers, and targeting SGO1 with siRNA and shRNA reduced the levels of SGO1, proliferation and metastasis of cancers.
Insights
Shugoshin 1 (SGO1) is highly expressed in many cancers, promoting proliferation and metastasis. Targeting SGO1 with siRNA/shRNA effectively reduces cancer growth and increases sensitivity to chemotherapy.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Shugoshin 1 (SGO1) is crucial for centromere protection and chromosome segregation during cell division.
- Altered SGO1 expression is linked to various cancers and genetic disorders, indicating its therapeutic potential.
Purpose of the Study:
- To review the literature on SGO1 gene and protein expression in diverse cancer models.
- To evaluate the efficacy of targeting SGO1 using siRNA/shRNA in cancer therapy.
Main Methods:
- Literature review of SGO1 expression in cancer cell lines, animal models, and patient tissues.
- Analysis of SGO1 targeting using small interfering RNA (siRNA) and short hairpin RNA (shRNA).
Main Results:
- Elevated SGO1 mRNA and protein levels were observed across multiple cancer types (prostate, renal, lung, breast, etc.), correlating with increased proliferation, invasion, and metastasis.
- SGO1 knockout/haploinsufficiency in mice led to chromosome instability and tumorigenesis.
- Higher SGO1 expression in patient tumors correlated with advanced stage, grade, size, and hormonal status, and was associated with chemoresistance.
- SGO1 knockdown via siRNA/shRNA reduced cancer cell proliferation, induced apoptosis, and enhanced sensitivity to chemotherapeutic agents.
Conclusions:
- SGO1 is significantly upregulated in various cancers, acting as a driver of tumor progression.
- Targeting SGO1 with siRNA/shRNA represents a promising therapeutic strategy to inhibit cancer growth, metastasis, and overcome chemoresistance.
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