TFIIB‐related factor 1 (Brf1) modulates the transcription of RNA Pol III genes (polymerase‐dependent genes). Upregulation of Pol III genes enhances tRNA and 5S RNA production and increases the translational capacity of cells to promote cell transformation and tumor development. However, the significance of Brf1 overexpression in human breast cancer (HBC) remains to be investigated. Here, we investigate whether Brf1 expression is increased in the samples of HBC, and we explore its molecular mechanism and the significance of Brf1 expression in HBC. Two hundred and eighteen samples of HBC were collected to determine Brf1 expression by cytological and molecular biological approaches. We utilized colocalization, coimmunoprecipitation, and chromatin immunoprecipitation methods to explore the interaction of Brf1 with estrogen receptor alpha (ERα). We determined how Brf1 and ERα modulate Pol III genes. The results indicated that Brf1 is overexpressed in most cases of HBC, which is associated with an ER‐positive status. The survival period of the cases with high Brf1 expression is significantly longer than those with low levels of Brf1 after hormone treatment. ERα mediates Brf1 expression. Brf1 and ERα are colocalized in the nucleus. These results indicate an interaction between Brf1 and ERα, which synergistically regulates the transcription of Pol III genes. Inhibition of ERα by its siRNA or tamoxifen reduces cellular levels of Brf1 and Pol III gene expression and decreases the rate of colony formation of breast cancer cells. Together, these studies demonstrate that Brf1 is a good biomarker for the diagnosis and prognosis of HBC. This interaction of Brf1 with ERα and Brf1 itself are potential therapeutic targets for this disease.
The levels of the products of RNA polymerase III-dependent genes (Pol III genes), including tRNAs and 5S rRNA, are elevated in transformed and tumor cells, which potentiate tumorigenesis. TFIIB-related factor 1 (Brf1) is a key transcription factor and specifically regulates the transcription of Pol III genes. In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces Pol III gene transcription and is sufficient for inhibiting cell transformation and tumor formation. Emerging evidence indicates that dysregulation of Brf1 and Pol III genes is linked to the development of hepatocellular carcinoma (HCC) in humans and animals. We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals. This review summarizes the effects of dysregulation of these genes on HCC and their regulation by signaling pathways and epigenetics. These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients.
In this study, we conducted molecular identification and complete mitochondrial genome annotation of isopod parasites isolated from mud crabs (Scylla paramamosain) in the China Sea. The specimen was identified as Portunion sinensis, a recently described species of the family Entoniscidae. P. sinensis is characterized by an anterior thorax positioned vertically and posterior ventral processes directed backwards; the female’s marsupium is formed by the close adhesion of oostegites to the host membrane; the first oostegite is differentiated into three parts; the pleopoda have well-developed lamellar and pleural lamellae; and two ventral ovarian processes are present along with a pair of dorsal processes. The complete mitochondrial genome of the parasite is 14,603 bp in length, containing 35 genes (13 protein-coding genes, 20 transfer RNAs, and 2 ribosomal RNAs) as well as a putative control region (CR) located between the cob and nad1 genes. This study represents the initial characterization of the mitochondrial genome of P. sinensis. These findings provide molecular validation of its status as an independent species and lay the groundwork for the future identification of parasites within the genus Portunion. These data provide a necessary molecular reference for future research into the systematics and evolutionary history of decapod-infesting parasites.