AI Article Synopsis
- Transcriptional repression of the UBB gene is a specific cancer alteration found in many patients with female reproductive tract cancers, particularly high-grade serous ovarian cancer.
- Approximately 30% of HGSOC patients exhibit UBB repression, which makes them heavily reliant on the gene UBC for ubiquitin production.
- Research involving ovarian tumor cell lines showed that targeting UBC can lead to tumor regression and improved survival, highlighting the potential of UBC as a therapeutic target for patients with UBB silencing.
Article Abstract
Transcriptional repression of ubiquitin B (UBB) is a cancer-subtype-specific alteration that occurs in a substantial population of patients with cancers of the female reproductive tract. UBB is 1 of 2 genes encoding for ubiquitin as a polyprotein consisting of multiple copies of ubiquitin monomers. Silencing of UBB reduces cellular UBB levels and results in an exquisite dependence on ubiquitin C (UBC), the second polyubiquitin gene. UBB is repressed in approximately 30% of high-grade serous ovarian cancer (HGSOC) patients and is a recurrent lesion in uterine carcinosarcoma and endometrial carcinoma. We identified ovarian tumor cell lines that retain UBB in a repressed state, used these cell lines to establish orthotopic ovarian tumors, and found that inducible expression of a UBC-targeting shRNA led to tumor regression, and substantial long-term survival benefit. Thus, we describe a recurrent cancer-specific lesion at the level of ubiquitin production. Moreover, these observations reveal the prognostic value of UBB repression and establish UBC as a promising therapeutic target for ovarian cancer patients with recurrent UBB silencing.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707153 | PMC |
| http://dx.doi.org/10.1172/JCI92914 | DOI Listing |
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