| Autor: |
Noriega-Rivera R; Department of Biochemistry, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA.; Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA., Rivera-Serrano M; Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA.; Department of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan, PR 00931, USA., Rabelo-Fernandez RJ; Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA.; Department of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan, PR 00931, USA., Pérez-Santiago J; Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA.; School of Dental Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA., Valiyeva F; Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA., Vivas-Mejía PE; Department of Biochemistry, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA.; Comprehensive Cancer Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA. |
| Abstrakt: |
Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC. |
