Regulation of ZMYND8 to Treat Cancer

Abstract

Zinc finger myeloid, nervy, and deformed epidermal autoregulatory factor 1-type containing 8 (Zinc finger MYND-type containing 8, ZMYND8) is a transcription factor, a histone H3-interacting protein, and a putative chromatin reader/effector that plays an essential role in regulating transcription during normal cellular growth. Mutations and altered expression of ZMYND8 are associated with the development and progression of cancer. Increased expression of ZMYND8 is linked to breast, prostate, colorectal, and cervical cancers. It exerts pro-oncogenic effects in breast and prostate cancers, and it promotes angiogenesis in zebrafish, as well as in breast and prostate cancers. In contrast, downregulation of ZMYND8 is also reported in breast, prostate, and nasopharyngeal cancers. ZMYND8 acts as a tumor suppressor in breast and prostate cancers, and it inhibits tumor growth by promoting differentiation; inhibiting proliferation, cell-cycle progression, invasiveness, and metastasis; and maintaining the epithelial phenotype in various types of cancers. These data together suggest that ZMYND8 is important in tumorigenesis; however, the existing data are contradictory. More studies are necessary to clarify the exact role of ZMYND8 in tumorigenesis. In the future, regulation of expression/activity of ZMYND8 and/or its binding partners may become useful in treating cancer.

Anticancer Inhibitors

“…The review by Chen collects the literature evidence about both pro-oncogenic and tumor-suppressive effects of ZMYND8 (zinc finger myeloid, nervy, and deformed epidermal autoregulatory factor 1-type containing 8) in various types of cancer [ 15 ].…”

Refining epigenetic prediction of chronological and biological age

“…Hypomethylation at probes nearby these genes has been previously linked to increased mortality risk, be that all-cause or disease specific (e.g., cancer or, cardiovascularrelated mortality) 20,[68][69][70] . Other, non-smoking related, lead probes mapped to genes whose methylation has been linked to various forms of cancer, increased cardiometabolic risk, and age-related macular degeneration [25][26][27][28][29][30][31][32][33][34] . There was moderate agreement (correlation of 0.58 between Z scores) between our findings and the significant results from a previous EWAS meta-analysis of survival.…”

“…The lead findings included CpGs mapping to smoking-related loci 10,[20][21][22][23][24] such as cg05575921 (AHRR, p = 3.01 x 10 -57 ), cg03636183 (F2RL3, p = 6.78 x 10 -44 ), cg19859270 (GPR15, p = 1.09 x 10 -33 ), cg17739917 (RARA, p = 1.92 x 10 -33 ), cg14391737 (PRSS23, p = 5.59 x 10 -33 ), cg09935388 (GFI1, p = 3.30 x 10 -31 ), and cg25845814 (ELMSAN1/MIR4505, p = 1.31 x 10 -30 ) (Supplementary Table 7). Of the non-smoking-related CpGs amongst the top 50 associations, seven mapped to genes whose methylation has been linked to various forms of cancer, including ZMIZ1 25 , SOCS3 [26][27][28] , ZMYND8 29 and CHD5 [30][31][32] . Another probe mapped to FKBP5, a gene whose methylation is involved in the regulation of the stress response, and which has been linked to increased cardiometabolic risk through accelerated ageing 33 .…”

Protein Degradation by E3 Ubiquitin Ligases in Cancer Stem Cells

“…FBXW7 also interacts with ZMYND8, inducing its polyubiquitination and degradation [ 98 ]. ZMYND8 is an epigenetic regulator reported as an oncogene in several tumors [ 99 ]. Reduced FBXW7 expression promotes accumulated ZMYND8 protein and enhances tumor progression and stemness in bladder cancer [ 98 ].…”