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Identification of long noncoding RNAs with aberrant expression in prostate cancer metastases.
Sattari, Mina; Kohvakka, Annika; Moradi, Elaheh; Rauhala, Hanna; Urhonen, Henna; Isaacs, William B; Nykter, Matti; Murtola, Teemu J; Tammela, Teuvo L J; Latonen, Leena; Bova, G Steven; Kesseli, Juha; Visakorpi, Tapio.
Afiliación
  • Sattari M; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Kohvakka A; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Moradi E; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Rauhala H; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Urhonen H; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Isaacs WB; The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
  • Nykter M; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Murtola TJ; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Tammela TLJ; Department of Urology, Tampere University Hospital, Tampere, Finland.
  • Latonen L; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
  • Bova GS; Department of Urology, Tampere University Hospital, Tampere, Finland.
  • Kesseli J; Foundation for the Finnish Cancer Institute, Helsinki, Finland.
  • Visakorpi T; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Endocr Relat Cancer ; 30(8)2023 08 01.
Article en En | MEDLINE | ID: mdl-37140987
Prostate cancer (PCa) is the second-most common cause of male cancer-related death in western industrialized countries, and the emergence of metastases is a key challenge in the treatment of PCa. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play an important role in the regulation of diverse cellular and molecular processes during the development and progression of cancer. Here, we utilized a unique cohort of castration-resistant prostate cancer metastases (mCRPC) and corresponding localized tumors and RNA sequencing (RNA-seq). First, we showed that patient-to-patient variability accounted for most of the variance in lncRNA expression between the samples, suggesting that genomic alterations in the samples are the main drivers of lncRNA expression in PCa metastasis. Subsequently, we identified 27 lncRNAs with differential expression (DE-lncRNAs) between metastases and corresponding primary tumors, suggesting that they are mCRPC-specific lncRNAs. Analyses of potential regulation by transcription factors (TFs) revealed that approximately half of the DE-lncRNAs have at least one binding site for the androgen receptor in their regulatory regions. In addition, TF enrichment analysis revealed the enrichment of binding sites for PCa-associated TFs, such as FOXA1 and HOXB13, in the regulatory regions of the DE-lncRNAs. In a cohort of prostatectomy-treated prostate tumors, four of the DE-lncRNAs showed association with progression-free time and two of them (lnc-SCFD2-2 and lnc-R3HCC1L-8) were independent prognostic markers. Our study highlights several mCRPC-specific lncRNAs that might be important in the progression of the disease to the metastatic stage and may also serve as potential biomarkers for aggressive PCa.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / ARN Largo no Codificante / Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans / Male Idioma: En Revista: Endocr Relat Cancer Asunto de la revista: ENDOCRINOLOGIA / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / ARN Largo no Codificante / Neoplasias de la Próstata Resistentes a la Castración Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans / Male Idioma: En Revista: Endocr Relat Cancer Asunto de la revista: ENDOCRINOLOGIA / NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Reino Unido