Zinc Finger And BTB Domain Containing 20 Research Articles

Recent topics on α‐fetoprotein

Zinc-fingers and homeoboxes 2 (ZHX2) and zinc-finger and BTB domain containing 20 (ZBTB20) repress the postnatal expression of α-fetoprotein (AFP) by interacting with the AFP gene promoter regions. ZHX2 inhibits the expression of AFP and cyclins A and E. ZBTB20 is negatively regulated by CUX1, which promotes cell-cycle progression, suggesting that AFP reactivation is closely linked to hepatocyte proliferation. A slight elevation in the serum AFP level often occurs in patients with chronic hepatitis C in the absence of hepatocellular carcinoma (HCC) and is an independent risk factor for HCC development to complement the fibrosis stage. In addition, the sustained elevation of AFP after interferon therapy is a risk factor of HCC development. AFP levels are clinically useful in predicting the outcomes of liver transplantation and sorafenib therapy for HCC patients. A low preoperative AFP level is a predictor of long-term survival and is associated with a low recurrence rate of HCC after liver transplantation. AFP response (≥20% decrease in AFP during 6-8 weeks of treatment) rather than radiological outcomes is a significant prognostic factor for survival in sorafenib-treated HCC patients. Highly sensitive Lens culinaris agglutinin-reactive AFP (AFP-L3) is 5-10 times more sensitive than conventional AFP-L3, and useful for early detection of HCC in patients with total AFP below 20 ng/mL.

Five Gastric Cancer-Susceptibility Loci Identified by Genome-Wide Association Studies

Gastric cancer is one of the most common cancers worldwide, especially in Asia, and ranks fourth in cancer death worldwide. Recently, in order to identify genes related to gastric cancer susceptibility, three genome-wide association studies were conducted using Japanese or Chinese populations, which revealed 5 gastric cancer-susceptibility loci: chromosome 1q22, 3q13.31, 5p13.1, 8q24.3 and 10q23. Further statistical and biological studies unveiled the causal candidate genes for the association in each locus: Mucin 1 (MUC1), encoding a membrane protein, in 1q22; zinc finger and BTB domain containing 20 (ZBTB20), a transcription factor, in 3q13.31; protein kinase, AMP-activated, alpha 1 catalytic subunit (PRKAA1), a ser/thr protein kinase, and/or prostaglandin E receptor 4 (PTGER4), a prostaglandin E2 receptor, and other 3 genes, in 5p13; Prostate stem cell antigen (PSCA), a membrane protein, in 8q24; phospholipase C, epsilon 1 (PLCE1), a phospholipase, in 10q23. Among these genes, MUC1 and PSCA were biologically investigated to obtain some rational for their relation to gastric carcinogenesis; however, the function of the other genes in cancer development is yet to be uncovered. As the genes identified through the genome-wide association studies have a strong potential to open a new door in cancer research, further studies are anticipated to be performed to elucidate their function and molecular pathways for application of the products to the therapy and prevention of gastric cancer.

Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer

The human POK family members are transcription factors with a POZ domain and zinc fingers that act primarily as transcriptional repressors. Several members of this family are involved in oncogenesis and this prompted us to assess whether expression levels of individual POK family members are associated with clinical outcomes in cancer. We have observed that ZBTB4 is downregulated in breast cancer patients, and that its expression is significantly correlated with relapse-free survival. Further integrative analysis of mRNA and microRNA (miR) expression data from the NCI-60 cell lines revealed an inverse correlation between ZBTB4 and oncogenic miRs derived from the miR-17-92 cluster and its paralogues. The experimental results using MDA-MB-231 and MCF-7 human breast cancer cells confirm that miRNAs derived from these clusters, containing miR-17-5p, miR-20a, miR-106a, miR-106b and miR-93, negatively regulate ZBTB4 expression. Overexpression of ZBTB4 or restoration of ZBTB4 by using an antagomir inhibit growth and invasion of breast cancer cells, and this effect is due, in part, to ZBTB4-dependent repression of the specificity protein 1 (Sp1), Sp3, and Sp4 genes, and subsequent downregulation of several Sp-dependent oncogenes, in part, through competition between ZBTB4 and Sp transcription factors for GC-rich promoter sequences. These results confirm that ZBTB4 functions as a novel tumor suppressor gene with prognostic significance for breast cancer survival, and the oncogenic miR-17-92/ZBTB4/Sp axis may be a potential therapeutic target.