Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

Retrospective study on Professor Zhongying Zhou's experience in Traditional Chinese Medicine treatment on diabetic nephropathy

OBJECTIVE:To study and analyze the etiology and pathogenesis,diagnosis and prescription for cases of diabetic nephropathy(DN) treated by Professor Zhongying Zhou(Prof.Zhou) with the help of dada mining technique,so as to inherit his clinical experience and academic thoughts.METHODS:After pretreatment of the medical record information,statistical software SPSS 13.0 was used to analyze and process the standardized data using the descriptive analysis,cluster analysis and association rules.RESULTS:Ninety-four entries derived from Traditional Chinese Medicine(TCM) four-diagnostic information were selected.Through data mining,the highest frequency was yellow-thin-greasy tongue coating,followed by dark tongue,and then by thready-slippery pulse.The main self-conscious symptoms were limb numbness,dry mouth,frequent micturition,etc.With respect to pathogenesis,the etiology related to kidney reached 73.46%.The frequency of pathological factors for deficiency,blood stasis,heat,dampness,phlegm and dryness were 137.65%,80.25%,78.40%,48.77%,21.60%,and 14.20% respectively.A total of 236 kinds of herbs were used 2913 person times,averaging 17.98 herbs per prescription.CONCLUSION:The pathological location of DN is in the kidney.The pathogenesis of the disease is deficiency in origin and excess in superficiality,the former of which include deficiency of the liver and kidney,and deficiency of both Qi and Yin.The main pathological factors are blood stasis,heat,dampness,phlegm,and dryness;and they act upon each other to form the complex pathogenesis in terms of blood stasis-heat,dampness-heat,phlegm-heat,and dryness-heat.All the above factors are always crucial in the aggravation of DN throughout the whole course of its pathological evolution.

Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis

The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer.However,cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues.Here,we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples,including blood,normal tissue,para-cancer,polyp,and colorectal cancer.