The X-Linked Tumor Suppressor TSPX Regulates Genes Involved in the EGFR Signaling Pathway and Cell Viability to Suppress Lung Adenocarcinoma.

TSPX is an X-linked tumor suppressor that was initially identified in non-small cell lung cancer (NSCLC) cell lines. However, its expression patterns and downstream mechanisms in NSCLC remain unclear. This study aims to investigate the functions of TSPX in NSCLC by identifying its potential downstream targets and their correlation with clinical outcomes.

Androgen receptor variant 7 exacerbates hepatocarcinogenesis in a c-MYC-driven mouse HCC model.

Androgen receptor variant 7 (AR-V7), an AR isoform with a truncated ligand-binding domain, functions as a transcription factor in an androgen-independent manner. AR-V7 is expressed in a subpopulation of hepatocellular carcinoma (HCC), however, its role(s) in this cancer is undefined. In this study, we investigated the potential roles of AR-V7 in hepatocarcinogenesis in vivo in a c-MYC-driven mouse HCC model generated by the hydrodynamic tail-vein injection system.

Sex chromosome DSD individuals with mosaic 45,X0 and aberrant Y chromosomes in 46,XY cells: distinct gender phenotypes and germ cell tumour risks.

")," individuals with rearranged Y chromosome breaks in their 46,XY cells are reported with male and female gender phenotypes and differences in germ cell tumour (GCT) risk. This raised the question of whether male or female gender and GCT risk depends on the site of the break and/or rearrangement of the individual´s Y chromosome. In this paper, we report molecular mapping of the breakpoint on the aberrant Y chromosome of 22 individuals with a 45,X/46,XY karyotype reared with a different gender.

The 2020 Ming K. Jeang awards for excellence in Cell & Bioscience.

Three articles published by the research groups led by Yun-Bo Shi of the National Institute of Child Health and Human Development, National Institutes of Health, USA; Aria Baniahmad of the Institute of Human Genetics, Jena University Hospital, Germany; and Kuanyu Li of the Nanjing University Medical School, China, have been selected as the recipients of the 2020 Ming K. Jeang Award for Excellence in Cell and Bioscience.

The 2019 Ming K. Jeang awards for excellence in .

Two articles published by the research groups led by You-Shuo Liu of the Central South University, Changsha, Hunan, and Min Fang of the Huazhong University of Science and Technology, Wuhan, China have been selected as the recipients of the 2019 Ming K. Jeang Award for Excellence in Cell & Bioscience.

Y chromosome in health and diseases.

Sex differences are prevalent in normal development, physiology and disease pathogeneses. Recent studies have demonstrated that mosaic loss of Y chromosome and aberrant activation of its genes could modify the disease processes in male biased manners. This mini review discusses the nature of the genes on the human Y chromosome and identifies two general categories of genes: those sharing dosage-sensitivity functions with their X homologues and those with testis-specific expression and functions.

Potential dual functional roles of the Y-linked RBMY in hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is a highly heterogeneous liver cancer with significant male biases in incidence, disease progression, and outcomes. Previous studies have suggested that genes on the Y chromosome could be expressed and exert various male-specific functions in the oncogenic processes. In particular, the RNA-binding motif on the Y chromosome (RBMY) gene is frequently activated in HCC and postulated to promote hepatic oncogenesis in patients and animal models.

The Y-linked proto-oncogene TSPY contributes to poor prognosis of the male hepatocellular carcinoma patients by promoting the pro-oncogenic and suppressing the anti-oncogenic gene expression.

Background: Liver cancer is one of the major causes of cancer death worldwide, with significantly higher incidence and mortality among the male patients. Although sex hormones and their receptors could contribute to such sex differences, the story is incomplete. Genes on the male-specific region of the Y chromosome could play a role(s) in this cancer.

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis.

The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures.

Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.

Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse.

The Y-located proto-oncogene TSPY exacerbates and its X-homologue TSPX inhibits transactivation functions of androgen receptor and its constitutively active variants.

The gonadoblastoma gene, testis-specific protein Y-encoded (TSPY), on the Y chromosome and its X-homologue, TSPX, are cell cycle regulators and function as a proto-oncogene and a tumor suppressor respectively in human oncogenesis. TSPY and TSPX competitively bind to the androgen receptor (AR) and AR variants, such as AR-V7, at their conserved SET/NAP domain, and exacerbate and repress the transactivation of the AR/AR-V7 target genes in ligand dependent and independent manners respectively. The inhibitory domain has been mapped to the carboxyl acidic domain of TSPX, truncation of which renders TSPX to be stimulatory while its transposition to the C-terminus of TSPY results in an inhibitory hybrid protein.

Identification of a TSPY co-expression network associated with DNA hypomethylation and tumor gene expression in somatic cancers.

Testis specific protein Y-encoded (TSPY) is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown.

Functional role of DNA mismatch repair gene PMS2 in prostate cancer cells.

DNA mismatch repair (MMR) enzymes act as proofreading complexes that maintains genomic integrity and MMR-deficient cells show an increased mutation rate. MMR has also been shown to influence cell signaling and the regulation of tumor development. MMR consists of various genes and includes post-meiotic segregation (PMS) 2 which is a vital component of mutL-alpha.

Epigenetic gene silencing by the SRY protein is mediated by a KRAB-O protein that recruits the KAP1 co-repressor machinery.

The sex determination transcription factor SRY is a cell fate-determining transcription factor that mediates testis differentiation during embryogenesis. It may function by repressing the ovarian determinant gene, RSPO1, action in the ovarian developmental pathway and activates genes, such as SOX9, important for testis differentiation at the onset of gonadogenesis. Further, altered expression of SRY and related SOX genes contribute to oncogenesis in many human cancers.