TY - JOUR
T1 - What do we have to know about pd-l1 expression in prostate cancer? A systematic literature review. part 5: Epigenetic regulation of pd-l1
AU - Palicelli, Andrea
AU - Croci, Stefania
AU - Bisagni, Alessandra
AU - Zanetti, Eleonora
AU - De Biase, Dario
AU - Melli, Beatrice
AU - Sanguedolce, Francesca
AU - Ragazzi, Moira
AU - Zanelli, Magda
AU - Chaux, Alcides
AU - Cañete-Portillo, Sofia
AU - Bonasoni, Maria Paola
AU - Soriano, Alessandra
AU - Ascani, Stefano
AU - Zizzo, Maurizio
AU - Ruiz, Carolina Castro
AU - De Leo, Antonio
AU - Giordano, Guido
AU - Landriscina, Matteo
AU - Carrieri, Giuseppe
AU - Cormio, Luigi
AU - Berney, Daniel M.
AU - Gandhi, Jatin
AU - Nicoli, Davide
AU - Farnetti, Enrico
AU - Santandrea, Giacomo
AU - Bonacini, Martina
N1 - Funding Information:
Acknowledgment: Andrea Palicelli thanks his family for personal support. supported by ORCID and a PCUK grant.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
PY - 2021/11/15
Y1 - 2021/11/15
N2 - 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.
AB - 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.
KW - Cancer
KW - Checkpoint inhibitors
KW - DNA methylation
KW - Epigenetic
KW - Immunotherapy
KW - MiRNA
KW - PD-L1
KW - Prostate
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U2 - 10.3390/ijms222212314
DO - 10.3390/ijms222212314
M3 - Review article
AN - SCOPUS:85118936487
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 22
M1 - 12314
ER -