Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

Abstract

Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

T2DB: A Web Database for Long Non-Coding RNA Genes in Type II Diabetes

“…Although some differentially expressed genes were shared between T2D and control samples ( Figure 3 B), 181 up- and 179 down-regulated genes were differentially regulated specifically in T2D compared to the control samples, including 35 up- and 22 down-regulated lncRNA genes ( Supplementary Table S6 ). Among these up-regulated lncRNA genes, only the following nine have been previously studied: (1) ENSG00000232855 (novel transcript) [ 75 ]; (2) ENSG00000272512 (novel transcript) [ 76 ]; (3) KCNJ2 antisense RNA 1 (KCNJ2-AS1) [ 77 , 78 , 79 ]; (4) KLHDC7B divergent transcript (KLHDC7B-DT) [ 80 , 81 , 82 ]; (5) long intergenic non-protein-coding RNA 2015 (LINC02015) [ 83 , 84 ]; (6) long intergenic non-protein-coding RNA 2381 (LINC02381) [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]; (7) long intergenic non-protein-coding RNA 2541 (LINC02541) [ 94 ]; (8) serpin family B member 9 pseudogene 1 (SERPINB9P1) [ 95 , 96 , 97 ]; and (9) USP30 antisense RNA 1 (USP30-AS1) [ 98 , 99 , 100 ]. However, only the functions of the lncRNA genes LINC02381 and USP30_AS1 are known, with the former known to bind transcription factors [ 85 ], RNA-binding proteins [ 86 ], and miRNAs [ 87 , 88 , 89 , 90 , 91 , 92 , 93 ]; while USP30-AS1 acts as a miRNA sponge [ 98 , 99 ] and is involved in the cis-regulation of the nearby protein-coding genes USP30 and ANKRD13A [ 100 ].…”

“…(2) ENSG00000272512 (novel transcript) [76]; (3) KCNJ2 antisense RNA 1 (KCNJ2-AS1) [77][78][79]; (4) KLHDC7B divergent transcript (KLHDC7B-DT) [80][81][82]; (5) long intergenic non-proteincoding RNA 2015 (LINC02015) [83,84]; (6) long intergenic non-protein-coding RNA 2381 (LINC02381) [85][86][87][88][89][90][91][92][93]; (7) long intergenic non-protein-coding RNA 2541 (LINC02541) [94]; (8) serpin family B member 9 pseudogene 1 (SERPINB9P1) [95][96][97]; and (9) USP30 antisense RNA 1 (USP30-AS1) [98][99][100]. However, only the functions of the lncRNA genes LINC02381 and USP30_AS1 are known, with the former known to bind transcription factors [85], RNA-binding proteins [86], and miRNAs [87][88][89][90][91][92][93]; while USP30-AS1 acts as a miRNA sponge [98,99] and is involved in the cis-regulation of the nearby protein-coding genes USP30 and ANKRD13A [100].…”