The Role of LSD1 and LSD2 in Cancers of the Gastrointestinal System: An Update

Abstract

Epigenetic mechanisms are known to play a key role in cancer progression. Specifically, histone methylation involves reversible post-translational modification of histones that govern chromatin structure remodelling, genomic imprinting, gene expression, DNA damage repair, and meiotic crossover recombination, among other chromatin-based activities. Demethylases are enzymes that catalyse the demethylation of their substrate using a flavin adenine dinucleotide-dependent amine oxidation process. Lysine-specific demethylase 1 (LSD1) and its homolog, lysine-specific demethylase 2 (LSD2), are overexpressed in a variety of human cancer types and, thus, regulate tumour progression. In this review, we focus on the literature from the last 5 years concerning the role of LSD1 and LSD2 in the main gastrointestinal cancers (i.e., gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer).

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“…During inflammation, LSD1 can act as both a pro-inflammatory and anti-inflammatory epigenetic regulator [ 42 ]. LSD1 can have pro-inflammatory effects, and upregulation can contribute to rheumatoid arthritis, sepsis, hepatitis B virus-associated glomerulonephritis (HBV-GN) and SARS-CoV-2 infection, as well as tumor progression [ 157 ]. It needs to be clarified which of these effects are mediated by MR, as LSD1 acts as coregulator for several NRs.…”

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“…Lysine-specific demethylase 1 (LSD1) is a flavin-dependent lysine-specific histone demethylase first identified in 2004 and mediated transcriptional activation or repression via erasing methyl groups from H3K9me2/1 and H3K4me2/1, respectively (Figure 1) (Shi et al, 2004;Fang et al, 2020;Kim et al, 2021;Malagraba et al, 2022;Song et al, 2022). Recently studies found that LSD1 could also remove the methyl groups from several non-histone proteins such as ERα, MTA1, HIF-1α, AGO2, HSP90, MEFD2, and STAT3 and be involved in many cancer cell events (Majello et al, 2019).…”