The Function And Regulation Mechanism Of Histone Demethylase KDM7A In Luminal Breast Cancer

1.Research background and significanceBreast cancer is the most common malignant tumor in women,ranking the first in the incidence of female malignant tumors in China,and seriously endangers women’s physical and mental health.The most common type of breast cancer is Luminal breast cancer,accounting for 60%to 70%.Because of the positive expression of estrogen receptor(ER),the anti-estrogen drug tamoxifen is usually used for endocrine therapy.The occurrence of breast cancer is often accompanied by genetic and epigenetic changes,and epigenetic regulation may have potential therapeutic and prognostic effects on breast cancer.In epigenetics,histone modification can change the loosening or agglutinating state of chromatin by affecting the affinity between histone and DNA double strands,or play a role in gene transcription regulation by affecting the affinity between other transcription factors and structural gene promoters.Lysine demethylation is one of the common modification methods of histone.At present,more than 20 kinds of histone lysine demethylases(KDMs)have been found in the human genome,which are mainly divided into lysine specific demethylases(Lysine specific demethylases).LSD)and Jmjc(Jumonji domain-containing protein).Histone demethylase KDM7A is a class of enzymes that can remove the modification of histone methylation.As a newly discovered histone demethylase in recent years,it can specifically act on H3K9me2 and H3K27me2 sites and belongs to the Jmjc family of histone demethylases.The latest study found that KDM7A can maintain the dryness of triple negative breast cancer cells and inhibit apoptosis.After knockdown of KDM7A in SUM159PT and MDA-MB-231 breast cancer cells,the dry function of triple negative breast cancer cells was significantly reduced.KDM7A knockdown also promoted apoptosis by down-regulating the level of apoptosis-related factor Bcl2 and the phosphorylation of Bad in triple-negative breast cancer cells.However,the results of CCK-8,plate cloning and soft AGAR culture showed that KDM7A did not affect the proliferation of triple negative breast cancer cells.However,another study showed that in hormone-sensitive prostate cancer,KDM7A interacted with androgen receptor(AR)to promote the proliferation of cancer cells.Based on the above research background,to explore the new functions and regulatory mechanisms of KDM7A in estrogen-receptor-positive Luminal breast cancer may serve as a new direction for the treatment of estrogen-receptor-positive breast cancer and provide new ideas for the clinical treatment of patients with Luminal breast cancer.2.Main research contents of this paperIn this study,the function and regulatory mechanism of KDM7A in estrogen-receptor-positive Luminal breast cancer were studied.First,whether there are endogenous and exogenous interactions between hiprotein demethylase KDM7A and estrogen receptor ERa in estrogen-receptor-positive Luminal breast cancer,and whether the interaction will change after the addition of estradiol.Secondly,whether KDM7A has an effect on the proliferation of Luminal type breast cancer cells.Finally,the mechanism of the effect of KDM7A on the proliferation of Luminal type breast cancer cells was discussed.3.ResultsThrough the study of the function and mechanism of KDM7A on Luminal breast cancer,we have drawn the following conclusions:(1)There is an interaction between histone demethylase KDM7A and estrogen receptor ERα,and the interaction between them will be enhanced in the presence of estradiol.(2)The histone demethylase KDM7A stimulated by estradiol inhibited the proliferation of Luminal type breast cancer cells;(3)Under estradiol stimulation,histone demethylase KDM7A inhibited the expression of ERa target genes MMP3,PCP4 and PDZK1.4.ConclusionThe histone demethylase KDM7A interacts with estrogen receptor ERα,and the interaction is enhanced under the stimulation of estradiol,inhibiting the expression of ERa target genes MMP3,PCP4 and PDZK1,thus inhibiting the proliferation of Luminal type breast cancer cells.Our study illustrates a new role of KDM7A in the regulation of proliferation of Luminal type breast cancer cells.Figure[8]table[5]reference[22]...