| Autor: |
Balcerak A; Department of Pathology and Anatomical Sciences, State University of New York, Buffalo, NY 14203, USA.; Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland., Szafron LA; Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland., Rubel T; Institute of Radioelectronics and Multimedia Technology, Warsaw University of Technology, 00-665 Warsaw, Poland., Swiderska B; Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland., Bonna AM; Triple Helical Peptides Ltd., Cambridge CB22 5DU, UK., Konarzewska M; Department of Forensic Medicine, Warsaw Medical University, 02-007 Warsaw, Poland., Sołtyszewski I; Department of Forensic Medicine, Warsaw Medical University, 02-007 Warsaw, Poland., Kupryjanczyk J; Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland., Szafron LM; Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. |
| Abstrakt: |
CRNDE is considered an oncogene expressed as long non-coding RNA. Our previous paper is the only one reporting CRNDE as a micropeptide-coding gene. The amino acid sequence of this micropeptide (CRNDEP) has recently been confirmed by other researchers. This study aimed at providing a mass spectrometry (MS)-based validation of the CRNDEP sequence and an investigation of how the differential expression of CRNDE(P) influences the metabolism and chemoresistance of ovarian cancer (OvCa) cells. We also assessed cellular localization changes of CRNDEP, looked for its protein partners, and bioinformatically evaluated its RNA-binding capacities. Herein, we detected most of the CRNDEP sequence by MS. Moreover, our results corroborated the oncogenic role of CRNDE , portraying it as the gene impacting carcinogenesis at the stages of DNA transcription and replication, affecting the RNA metabolism, and stimulating the cell cycle progression and proliferation, with CRNDEP being detected in the centrosomes of dividing cells. We also showed that CRNDEP is located in nucleoli and revealed interactions of this micropeptide with p54, an RNA helicase. Additionally, we proved that high CRNDE(P) expression increases the resistance of OvCa cells to treatment with microtubule-targeted cytostatics. Furthermore, altered CRNDE(P) expression affected the activity of the microtubular cytoskeleton and the formation of focal adhesion plaques. Finally, according to our in silico analyses, CRNDEP is likely capable of RNA binding. All these results contribute to a better understanding of the CRNDE(P) role in OvCa biology, which may potentially improve the screening, diagnosis, and treatment of this disease. |
