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.

What do we have to know about pd-l1 expression in prostate cancer? A systematic literature review. part 5: Epigenetic regulation of pd-l1 / Palicelli, A.; Croci, S.; Bisagni, A.; Zanetti, E.; De Biase, D.; Melli, B.; Sanguedolce, F.; Ragazzi, M.; Zanelli, M.; Chaux, A.; Canete-Portillo, S.; Bonasoni, M. P.; Soriano, A.; Ascani, S.; Zizzo, M.; Ruiz, C. C.; De Leo, A.; Giordano, G.; Landriscina, M.; Carrieri, G.; Cormio, L.; Berney, D. M.; Gandhi, J.; Nicoli, D.; Farnetti, E.; Santandrea, G.; Bonacini, M.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:22(2021), pp. 12314-12339. [10.3390/ijms222212314]

What do we have to know about pd-l1 expression in prostate cancer? A systematic literature review. part 5: Epigenetic regulation of pd-l1

Melli B.;Ragazzi M.;Zizzo M.;Giordano G.;Landriscina M.;Santandrea G.;
2021

Abstract

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.
2021
22
22
12314
12339
What do we have to know about pd-l1 expression in prostate cancer? A systematic literature review. part 5: Epigenetic regulation of pd-l1 / Palicelli, A.; Croci, S.; Bisagni, A.; Zanetti, E.; De Biase, D.; Melli, B.; Sanguedolce, F.; Ragazzi, M.; Zanelli, M.; Chaux, A.; Canete-Portillo, S.; Bonasoni, M. P.; Soriano, A.; Ascani, S.; Zizzo, M.; Ruiz, C. C.; De Leo, A.; Giordano, G.; Landriscina, M.; Carrieri, G.; Cormio, L.; Berney, D. M.; Gandhi, J.; Nicoli, D.; Farnetti, E.; Santandrea, G.; Bonacini, M.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:22(2021), pp. 12314-12339. [10.3390/ijms222212314]
Palicelli, A.; Croci, S.; Bisagni, A.; Zanetti, E.; De Biase, D.; Melli, B.; Sanguedolce, F.; Ragazzi, M.; Zanelli, M.; Chaux, A.; Canete-Portillo, S.; Bonasoni, M. P.; Soriano, A.; Ascani, S.; Zizzo, M.; Ruiz, C. C.; De Leo, A.; Giordano, G.; Landriscina, M.; Carrieri, G.; Cormio, L.; Berney, D. M.; Gandhi, J.; Nicoli, D.; Farnetti, E.; Santandrea, G.; Bonacini, M.
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