SNF2L maintains glutathione homeostasis by initiating SLC7A11 transcription through chromatin remodeling.

SNF2L encodes an ISWI chromatin remodeling factor that promotes gene transcription and is consistently elevated in cancers. Previous studies have shown that inhibiting SNF2L expression in cancer cells leads to significant growth suppression, DNA damage, and cell death. However, the underlying mechanisms remain poorly understood.

ERα prevents tumorigenesis of both liver and breast cancer cells through CCN5.

Estrogen receptor alpha (ERα)-mediated estrogen signaling has also shown to prevent hepatic tumorigenesis in mice. Consistent with this, hormone replacement therapy with estrogen supplementation dramatically reduced the risk of hepatocellular carcinoma. Silencing of ERα is also a key event for the transformation of ERα-positive breast cancer cells into malignant triple-negative breast cancer cells.

PRMT5 determines the pattern of polyploidization and prevents liver from cirrhosis and carcinogenesis.

Human hepatocellular carcinoma (HCC) occurs almost exclusively in cirrhotic livers. Here, we report that hepatic loss of protein arginine methyltransferase 5 (PRMT5) in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way. Furthermore, pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver.

Sexual dimorphism in the incidence of human cancers.

Background: Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers.

NUCLIZE for quantifying epigenome: generating histone modification data at single-nucleosome resolution using genuine nucleosome positions.

Background: Defining histone modification at single-nucleosome resolution provides accurate epigenomic information in individual nucleosomes. However, most of histone modification data deposited in current databases, such as ENCODE and Roadmap, have low resolution with peaks of several kilo-base pairs (kb), which due to the technical defects of regular ChIP-Seq technology.

Results: To generate histone modification data at single-nucleosome resolution, we developed a novel approach, NUCLIZE, using synergistic analyses of histone modification data from ChIP-Seq and high-resolution nucleosome mapping data from native MNase-Seq.

A sex-dimorphic mouse model of esophageal squamous cell carcinoma.

Sexual dimorphism in the incidence of human esophageal cancer, including both esophageal adenocarcinoma and squamous cell carcinoma, shows male dominancy. However, the mechanisms that underlie sexual dimorphism of esophageal cancer have been understudied in vivo due to the lack of sex-dimorphic mouse models. Here, we developed a sex-dimorphic mouse model of esophageal squamous cell carcinoma (ESCC) using a lower amount of 4-nitroquinoline-1-oxide (4-NQO) and a shorter latency of tumorigenesis compared to the traditional carcinogenesis procedures.

Genetic ablation of mammary ducts through foxa1 prevents breast cancer occurrence.

Risk reducing mastectomy is the only surgical approach for the prevention of breast cancer in women with deleterious genetic mutations or in those deemed to be at extremely high risk. However, up to 10.5% of these women still developed breast cancer.

Regulation of sex hormone receptors in sexual dimorphism of human cancers.

Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling.

Genomics of sex hormone receptor signaling in hepatic sexual dimorphism.

The liver plays a crucial role in a variety of physiological processes. Sexual dimorphism is markedly defined in liver disorders, such as fatty liver diseases and liver cancer, but barely addressed in the normal liver. Distinct sex hormone signaling between male and female livers is the major driving factor for hepatic sexual dimorphism.