Progress of synergistic factors of histone lysine specific demethylase 1 in colorectal cancer / 肿瘤研究与临床

ABSTRACT

The expression of histone lysine-specific demethylase 1 (LSD1) in colorectal cancer cells is increased, and LSD1 is closely related to its occurrence, development, proliferation, invasion and metastasis. LSD1 is a demethylase whose function depends on flavin adenine dinucleoside. It can specifically catalyze the demethylation reaction of histone lysine, and regulate the expression of target genes by reaction of demethyl and dimethyl (H3K4me, H3K4me2, H3K9me, and H3K9me2) at the 4th and 9th positions of lysine H3. Targeted inhibition of LSD1 has been proved to be able to exert significant anti-tumor effect, but since the tumors involve multiple centers and factors, later studies have found that single inhibition of LSD1 cannot completely and effectively kill tumor cells. Moreover, the specificity of the LSD1 catalytic substrate depends to a large extent on the synergistic factors that bind to it and form complexes. The double-target inhibitors based on LSD1 shows more remarkable effect in tumor inhibition. Therefore, finding the combined synergistic factors of LSD1 may provide the basis for the research of multi-target inhibitors.