Omics-Based Identification of Shared and Gender Disparity Routes in Hras12V-Induced Hepatocarcinogenesis: An Important Role for Dlk1-Dio3 Genomic Imprinting Region

The phenomenon of gender disparity is very profound in hepatocellular carcinoma (HCC). Although previous research has revealed important roles microRNA (miRNA) HCC, there are no studies investigating the role miRNAs observed hepatocarcinogenesis. In present study, we investigated global miRNAomics changes related to Ras -induced male-prevalent hepatocarcinogenesis a Hras12V -transgenic mouse model ( -Tg) by next-generation sequencing (NGS). We identified shared also unique miRNA expression profiles gender-dependent Two hundred sixty-four differentially expressed (DEMIRs) with q value ≤0.05 and fold change ≥2 were identified. A vertical comparison that lower numbers DEMIRs hepatic tumor (T) compared peri-tumor precancerous tissue (P) -Tg normal liver wild-type C57BL/6J mice (W) males indicated more susceptible develop HCC. pattern analysis 43 common HCC-related 4 -positive-related between females. By integrating mRNA transcriptomic data using 3-node FFL analysis, group significant components commonly contributing HCC sexes filtered out. horizontal showed majority located Dlk1-Dio3 genomic imprinting region (GIR) they closely not only tumorigenesis but This achieved regulating multiple metabolic pathways, including retinol, bile acid, steroid hormones. conclusion, identification provides valuable insights into mechanisms contribute male-biased carcinogenesis.