Interplay Between Epigenetic Modifiers and Transcription Factors in Driving Cancer Progression

Editorial

19 June 2023

Editorial: Interplay between epigenetic modifiers and transcription factors in driving cancer progression

Yongyong Yang

Annalisa Di Ruscio

Satoshi Inoue

Guocan Wang

and

Shuai Gao

1,801 views

0 citations

Editors

Shuai Gao

New York Medical College

Annalisa Di Ruscio

Beth Israel Deaconess Medical Center, Harvard Medical School

Guocan Wang

University of Texas MD Anderson Cancer Center

Satoshi Inoue

Tokyo Metropolitan Institute of Gerontology

Impact

Three subfamilies of CHD chromatin remodelers are presented with signature domains. The major functions of each domain are listed.

Review

26 January 2023

CHD1, a multifaceted epigenetic remodeler in prostate cancer

Haoyan Li

, 1 more and

Di Zhao

Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1’s roles in different contexts of prostate cancer, with an emphasis on its crosstalk with diverse signaling pathways. Furthermore, we highlight the potential therapeutic strategies for cancers with dysregulated CHD1. At last, we discuss current research gaps in understanding CHD1’s biological functions and molecular basis during disease progression, as well as the modeling systems for biology study and therapeutic development.

5,845 views

11 citations

(A) Identification of super-enhancers (16). The higher density of transcriptional regulators through cooperative binding to genomic regions contribute to both activated histone acetylation and higher transcriptional output at super-enhancers. K27: lysine 27. (B) Impacts of enhancer RNAs (eRNAs) at super-enhancers. Highly transcribed eRNAs facilitate formation of loop between promoters and enhancers.

Review

03 October 2022

Targeting phase separation on enhancers induced by transcription factor complex formations as a new strategy for treating drug-resistant cancers

Ken-ichi Takayama

and

Satoshi Inoue

6,939 views

8 citations

(A) Venn diagram for DHT-regulated genes in ARlow/DHThigh and ARhigh/DHTlow LNCaP-tet-AR cells and EZH2-regulated genes in LNCaP-ABL cells (fold-change > 1.5, adjusted P-value < 0.05). (B) Boxplot for AR/EZH2 co-target gene expression (68-genes) in LNCaP-tet-AR cells under indicated conditions. (C) qRT-PCR for ARhigh/DHTlow-unique AR regulated genes treated with 0.1 nM DHT and an EZH2 inhibitor, GSK126 (50μM for 24h). (D) Gene ontology of AR/EZH2 co-regulated 68 genes (FDR< 0.05). (E, F) AR/EZH2 co-target gene expression (68-gene) in TCGA, UW, and SU2C datasets (E) and Balk PCa dataset (F). (G) Kaplan-Meier survival analysis for the overall survival from the initiation of the first-line ARSi in mCRPC patients (SU2C cohort) with higher scores (purple, top 25%) of AR/EZH2 target signatures versus the lower scores (yellow, bottom 75%). (H) Immunoblotting for indicated proteins in LNCaP versus LNCaP-C4-2 cells. (I) Immunoblotting for indicated proteins in LNCaP-tet-AR cells immunoprecipitated with AR. (J) ChIP-qPCR of EZH2 at indicated AR binding sites. (K) Cell growth inhibition for LNCaP-tet-AR cells under the indicated conditions and treated with 30µM olaparib for 2d, or olaparib plus GSK126 (50 µM for 2d).

Original Research

03 November 2022

Increased AR expression in castration-resistant prostate cancer rapidly induces AR signaling reprogramming with the collaboration of EZH2

Maryam Labaf

, 9 more and

Changmeng Cai

3,057 views

11 citations

Original Research

12 July 2022

Driver Gene Alterations in Malignant Progression of Gastric Cancer

Yuanqiang Dong

, 4 more and

Jianjun Du

The identification of driver genes is of great importance in modern medical research. It is also an essential factor in the development of individualization and has a positive effect on understanding the causes of cancer. Gene mutations are the primary cause of the outcomes of the process of tumorigenesis. Driver genes can be used as therapeutic targets for tumor-specific mutation-dependent overexpression. This study sought to identify mutation-based driver genes in gastric cancer (GC) by applying comprehensive gene expression and copy number analysis. Multiplatform analysis was used to identify four major genomic subtypes of GC. The most prominent cancer-related variations observed in this cohort were TTN mutations (found in 56% of tumors), followed by TP53 (51%), MUC16 (7%), and LRP1B (6%) mutations. In our analysis, mutation characteristics were mainly related to the DNA mismatch repair system. In addition, 34 candidate driver oncogenes were identified in GC. Further research identified six GC-related driver genes associated with the levels of immune infiltration of different immune cells and the majority of immune markers. Our mutation-based study of driver oncogenes identified potential drug targets in GC.

2,918 views

8 citations