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Background: Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters.Methods: Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed.Results: Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006).Conclusions: Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%–11.2% (reference value 6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder.

BackgroundDespite zinc finger and BTB domain-containing 7A (ZBTB7A) documented importance in multiple tumors, the function and clinical value in Colorectal cancer (CRC) remain elusive. The aim of this study was to evaluate the functional roles and the clinical value of ZBTB7A in CRC progression.MethodsThe level of ZBTB7A was detected in a large cohort of CRC patients (n = 189) by immunohistochemistry (IHC), and we analyzed the diagnostic and prognostic value of the protein. In addition, the functional roles of ZBTB7A on CRC were explored in vitro and in vivo.ResultsSurvival analyses indicated that patients with high ZBTB7A expression made the prognosis worse (P = 0.024). Functionally, knockdown of ZBTB7A could markedly inhibit tumor proliferation in vitro and in vivo, whereas ZBTB7A overexpression displayed the opposite results.ConclusionsZBTB7A was associated with poor survival outcomes and functioned as an oncogene in CRC patients, indicating that it is a potential prognostic biomarker and therapeutic target for CRC patients.

Backgroud ZBTB protein is an important member of the C2H2 zinc finger protein family. As a transcription factor, it is widely involved in the transcriptional regulation of genes, cell proliferation, differentiation, and apoptosis. The ZBTB7A has been largely linked to different kinds of tumors due to its diverse function. However, the value for ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear. Methods In our work, we assessed the importance of ZBTB7A in UCEC. Firstly, Using Oncomine and Tumor Immunoassay Resource (TIMER) databases to evaluate the expression of ZBTB7A. Secondly, we explored the co-expression network of ZBTB7A through the cBioPortal online tool, Metascape, and LinkedOmics. TIMER was also used to explore the relationship between ZBTB7A and tumor immune invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CCK8, migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrial cancer cells. Results We found the ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expression of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers such as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Treg. Finally, we verified that ZBTB7A repressed E2F4 transcription and inhibited cells proliferation and migration. These results indicate that ZBTB7A may play a vital role in regulating immune cell infiltration in UCEC, and is a valuable prognostic marker. Conclusions In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, plays a vital role in regulating immune cell infiltration, possesses diagnostic and prognostic values and attenuates E2F4 transcription and cell proliferation, migration in vitro.

miR-372 has been shown a potent oncogenic miRNA in the pathogenesis of oral squamous cell carcinoma (OSCC). The zinc finger and BTB domain containing 7A protein (ZBTB7A) is a transcriptional regulator that is involved in a great diversity of physiological and oncogenic regulation. However, the modulation of ZBTB7A in OSCC remains unclear. Tissue analysis identifies a reverse correlation in expression between miR-372 and ZBTB7A in OSCC tumors. When OSCC cells have stable knockdown of ZBTB7A, their oncogenic potential and drug resistance is increased. By way of contrast, such an increase is attenuated by expression of ZBTB7A. Screening and validation confirms that ZBTB7A is able to modulate expression of the death receptors TRAIL-R1, TRAIL-R2, Fas and p53 phosphorylated at serine-15. In addition, ZBTB7A transactivates TRAIL-R2, which sensitizes cells to cisplatin-induced apoptosis. The ZBTB7A-TRAIL-R2 cascade is involved in both the extrinsic and intrinsic cisplatin-induced pathways of apoptosis. Database analysis indicates that the expression level of and the copy status of ZBTB7A and TRAIL-R2 are important survival predictors for head and neck cancers. Collectively, this study indicates the importance of the miR-372-ZBTB7A-TRAIL-R2 axis in mediating OSCC pathogenesis and in controlling OSCC drug resistance. Therefore, silencing miR-372 and/or upregulating ZBTB7A would seem to be promising strategies for enhancing the sensitivity of OSCC to cisplatin therapy.

SUMMARY Elevated levels of fetal globin protect against β-hemoglobinopathies, such as sickle cell disease and β-thalassemia. Two zinc-finger (ZF) repressors, BCL11A and ZBTB7A/LRF, bind directly to the fetal globin promoter elements positioned at −115 and −200, respectively. Here, we describe X-ray structures of the ZBTB7A DNA-binding domain, consisting of four adjacent ZFs, in complex with the −200 sequence element, which contains two copies of four consecutive C:G base pairs. ZF1 and ZF2 recognize the 5′ C:G quadruple, and ZF4 contacts the 3′ C:G quadruple. Natural non-coding DNA mutations associated with hereditary persistence of fetal hemoglobin (HPFH) impair ZBTB7A DNA binding, with the most severe disruptions resulting from mutations in the base pairs recognized by ZF1 and ZF2. Our results firmly establish ZBTB7A/LRF as a key molecular regulator of fetal globin expression and inform genome-editing strategies that inhibit repressor binding and boost fetal globin expression to treat hemoglobinopathies., Graphical abstract, In brief Yang et al. show that the transcription factor ZBTB7A has features that deviate from conventional one finger-three bases recognition. Among the four fingers, ZF1 and ZF2 each contact two DNA bases. ZF3 does not make base-specific contacts but serves as a spacer to position ZF4 into the right location.

The present study aimed to determine the association between changes in Zbtb7a expression levels and heterogeneity of nasopharyngeal carcinoma (NPC) CNE3 sublines. CNE3 sublines were established by screening of serial dilution and continuous passage. Proliferative ability and tumorigenicity of the sublines were analyzed separately by soft-agar colony formation and mouse studies. The NPC tissues from mice were analyzed by histological evaluation and immunohistochemistry. The expression levels of Zbtb7a mRNA and protein were analyzed separately by quantitative reverse transcription polymerase chain reaction and western blotting. According to findings from the soft-agar colony formation and mouse studies, two sublines with increased tumorigenicity compared with other sublines were transfected transiently with Zbtb7a short hairpin RNA (shRNA) recombinant plasmid. The changes in viability, migration and invasion abilities were evaluated separately by MTT, colorimetric focus-formation, Transwell migration and invasion assays. The sublines CNE3-GX6 and CNE3-GX11 were selected for subsequent study due to increased tumorigenicity and increased Zbtb7a expression levels compared with the other sublines. High metastatic potency was not observed in all of the sublines. Zbtb7a expression levels were positively associated with tumorigenic degree of the sublines. The growth, migration and invasion abilities of the sublines transfected with Zbtb7a shRNA plasmid were decreased compared with the cells transfected with empty vector in the negative control group. The findings suggest Zbtb7a expression levels may be associated with heterogeneity of CNE3 sublines. Therefore, Zbtb7a may have an important role in the regulatory mechanism of NPC heterogeneity.

// Dechao Jiao 1 , Yan Yan 2 , Shaofeng Shui 3 , Gang Wu 3 , JianZhuang Ren 3 , Yanli Wang 3 and Xinwei Han 3 1 Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China 2 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China 3 Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Correspondence to: Xinwei Han, email: rug025@163.com Keywords: MicroRNA-106b, chemoresistance, cholangiocarcinoma, 5-fluorouracil, Zbtb7a Received: January 12, 2017 Accepted: February 12, 2017 Published: May 02, 2017 ABSTRACT Background: Cholangiocarcinoma (CCA) is highly resistant to chemo-therapy, including 5-fluorouracil (5-FU) treatment. MicroRNAs are endogenous and short non-coding RNAs that can regulate multiple genes expression. Many microRNAs have shown functional roles in the chemo-resistance of tumors. Here, we examined the relationship between microRNAs expression and the sensitivity of CCA cells to 5-FU. Methods: Microarray analysis was used to determine the aberrantly expressed microRNAs in two 5-FU resistant CCA cell lines, KKU-M139 and KKU-M214 cells. To determine the effect of candidate microRNAs on 5-FU sensitivity, expression of candidate was modified via either transfection of a microRNA mimic or transfection of an antagonist. Ontology-based programs were also used to investigate the potential targets of microRNAs that were confirmed to affect the 5-FU sensitivity of CCA cells. Results: The microRNA-106b (miR-106b) was significantly down-regulated in 5-FU resistant CCA cells. Instead, over-expression of miR-106b could re-sensitize resistant CCA cells to 5-FU through down-regulation of Zbtb7a. Moreover, decreased expression of miR-106b is related to poor prognosis in patients with CCA, suggesting its potential role as a new prognostic marker in CCA. Conclusion: Our study demonstrates that miR-106b can reverse 5-FU resistance via Zbtb7a suppression, thus offer a novel and powerful strategy for CCA chemotherapy.

The large ZBTB family comprises a diverse group of transcriptional factors. Several ZBTB proteins have emerged as critical factors that regulate the lineage commitment, differentiation and function of lymphoid cells as well as many other developmental events. For instance, dysfunctions of ZBTB20 or ZBTB24 have been linked to multisystem failures in humans. Within the B-cell lineage, BCL6, ZBTB7A, ZBTB17 and ZBTB1 regulate the development/differentiation of B cells in both bone marrow and peripheral lymphoid organs, while ZBTB20 and ZBTB32 seem to mainly impact the maintenance of terminally-differentiated plasma cells. Given the importance of B cells in the prevention and treatment of infectious or autoimmune disorders, we herein summarize the roles of seven ZBTB family members (BCL6, ZBTB7A, ZBTB17, ZBTB20, ZBTB32, ZBTB1 and ZBTB24) in the development, differentiation and function of B cells as well as the underlying molecular mechanisms.