Advances in pancreatic cancer epigenetics: From the mechanism to the clinic

Table 1 Epigenetic characteristics of pancreatic cancer

Epigenetic mechanism	Key changes	Genes affected	Role in pancreatic cancer
DNA methylation	Hypermethylation of tumor suppressor genes, particularly in the promoter regions	p16, BRCA1, RASSF1A, CDKN2A, APC	DNA hypermethylation in the promoter regions of tumor suppressor genes (e.g., p16 and BRCA1) silences their expression, allowing for uncontrolled cell division, which leads to cancer initiation and progression. Methylation of CDKN2A and RASSF1A contributes to tumor resistance and poor prognosis
Histone modifications	Histone acetylation (activation) and deacetylation (silencing)	p21, p53, H3K9me, H3K27me, HDACs	Histone acetylation (activation) and deacetylation (silencing) affect the accessibility of DNA. In pancreatic cancer, HDACs are overexpressed, leading to silencing of tumor suppressor genes like p21 and p53, which promotes cell cycle dysregulation and tumor progression
Noncoding RNAs (miRNAs and lncRNAs)	Dysregulated expression of miRNAs and lncRNAs that impact tumor behavior	miR-21, miR-155, HOTAIR, MALAT1	Upregulation of miRNAs (e.g., miR-21 and miR-155) and lncRNAs (e.g., MALAT1 and HOTAIR) suppress tumor suppressor genes, promoting cancer cell proliferation, invasiveness, and metastasis by modulating gene expression
Chromatin remodeling	ATP-dependent chromatin remodeling complexes change chromatin structure, affecting gene transcription	SWI/SNF complex, BRG1	ATP-dependent chromatin remodeling complexes like SWI/SNF and BRG1 modify chromatin structure, making genes more or less accessible for transcription. In pancreatic cancer, the dysfunction or downregulation of these complexes leads to silencing of tumor suppressor genes, promoting cancer progression and metastasis

lncRNA: Long noncoding RNA.