What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1

International Journal of Molecular Sciences

Daniel M. Berney¹  Stefania Croci²  Martina Bonacini²  Carolina Castro Ruiz³  Jatin Gandhi⁴  Alessandra Soriano⁵  Sofia Cañete-Portillo⁶  Dario De Biase⁷  Alcides Chaux⁸  Giuseppe Carrieri⁹  Luigi Cormio⁹  Beatrice Melli^1,10  Guido Giordano^1,11  Matteo Landriscina^1,11  Davide Nicoli^1,12  Enrico Farnetti^1,12  Antonio De Leo^1,13  Stefano Ascani^1,14  Moira Ragazzi^1,15  Giacomo Santandrea^1,15  Maria Paola Bonasoni^1,15  Eleonora Zanetti^1,15  Alessandra Bisagni^1,15  Magda Zanelli^1,15  Andrea Palicelli^1,15  Francesca Sanguedolce^1,16  Maurizio Zizzo^1,17 

[1] Barts Cancer Institute, Queen Mary University of London, London EC1M 5PZ, UK;Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy;Department of Pathology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA;Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA;Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy;Department of Scientific Research, School of Postgraduate Studies, Norte University, Asunción 1614, Paraguay;Department of Urology and Renal Transplantation, University of Foggia, 71122 Foggia, Italy;Fertility Center, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy;Molecular Biology Laboratory, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Molecular Diagnostic Unit, Azienda USL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy;Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy;Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy;Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;

关键词: PD-L1;    prostate;    cancer;    epigenetic;    DNA methylation;    miRNA;   

DOI  :  10.3390/ijms222212314

来源: DOAJ

【 摘 要 】

Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the DNA sequence. Prostate cancer (PC) displays a complex genetic and epigenetic regulation of cell-growth pathways and tumor progression. We performed a systematic literature review (following PRISMA guidelines) focused on the epigenetic regulation of PD-L1 expression in PC. In PC cell lines, CpG island methylation of the CD274 promoter negatively regulated PD-L1 expression. Histone modifiers also influence the PD-L1 transcription rate: the deletion or silencing of the histone modifiers MLL3/MML1 can positively regulate PD-L1 expression. Epigenetic drugs (EDs) may be promising in reprogramming tumor cells, reversing epigenetic modifications, and cancer immune evasion. EDs promoting a chromatin-inactive transcriptional state (such as bromodomain or p300/CBP inhibitors) downregulated PD-L1, while EDs favoring a chromatin-active state (i.e., histone deacetylase inhibitors) increased PD-L1 expression. miRNAs can regulate PD-L1 at a post-transcriptional level. miR-195/miR-16 were negatively associated with PD-L1 expression and positively correlated to longer biochemical recurrence-free survival; they also enhanced the radiotherapy efficacy in PC cell lines. miR-197 and miR-200a-c positively correlated to PD-L1 mRNA levels and inversely correlated to the methylation of PD-L1 promoter in a large series. miR-570, miR-34a and miR-513 may also be involved in epigenetic regulation.

【 授权许可】

Unknown