Zinc Finger And BTB Domain-containing 7A Expression Research Articles

U3 snoRNA-mediated degradation of ZBTB7A regulates aerobic glycolysis in isocitrate dehydrogenase 1 wild-type glioblastoma cells.

The isocitrate dehydrogenase (IDH) phenotype is associated with reprogrammed energy metabolism in glioblastoma (GBM) cells. Small nucleolar RNAs (snoRNAs) are known to exert an important regulatory role in the energy metabolism of tumor cells. The purpose of this study was to investigate the role of C/D box snoRNA U3 and transcription factor zinc finger and BTB domain-containing 7A (ZBTB7A) in the regulation of aerobic glycolysis and the proliferative capacity of IDH1 wild-type (IDH1WT ) GBM cells. Quantitative reverse transcription PCR and western blot assays were utilized to detect snoRNA U3 and ZBTB7A expression. U3 promoter methylation status was analyzed via bisulfite sequencing and methylation-specific PCR. Seahorse XF glycolysis stress assays, lactate production and glucose consumption measurement assays, and cell viability assays were utilized to detect glycolysis and proliferation of IDH1WT GBM cells. We found that hypomethylation of the CpG island in the promoter region of U3 led to the upregulation of U3 expression in IDH1WT GBM cells, and the knockdown of U3 suppressed aerobic glycolysis and the proliferation ability of IDH1WT GBM cells. We found that small nucleolar-derived RNA (sdRNA) U3-miR, a small fragment produced by U3, was able to bind to the ZBTB4 3'UTR region and reduce ZBTB7A mRNA stability, thereby downregulating ZBTB7A protein expression. Furthermore, ZBTB7A transcriptionally inhibited the expression of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), which are key enzymes of aerobic glycolysis, by directly binding to the HK2 and LDHA promoter regions, thereby forming the U3/ZBTB7A/HK2 LDHA pathway that regulates aerobic glycolysis and proliferation of IDH1WT GBM cells. U3 enhances aerobic glycolysis and proliferation in IDH1WT GBM cells via the U3/ZBTB7A/HK2 LDHA axis.

ZBTB7A functioned as an oncogene in colorectal cancer

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.

Circular RNA Circ_0016760 Modulates Non-Small-Cell Lung Cancer Growth Through the miR-577/ZBTB7A Axis.

BackgroundPatients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) have a poor prognosis. Circular RNA circ_0016760 (circ_0016760) is associated with the development of NSCLC. At present, the role and regulatory mechanism of circ_0016760 in NSCLC have not been well explained.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was executed to detect the expression of circ_0016760, miR-577, and Zinc finger and BTB domain containing 7A (ZBTB7A) mRNA in NSCLC tissues and cells. The colony formation, migration, invasion, and extracellular acidification rate (ECAR) of NSCLC cells were determined through colony formation, transwell, or ECAR assays. The relationship between circ_0016760 or ZBTB7A and miR-577 was analyzed via dual-luciferase reporter and RNA pull-down or RNA immunoprecipitation (RIP) assays. Protein level of ZBTB7A was evaluated with Western blot analysis. Xenograft assay was conducted to confirm the role of circ_0016760 in vivo.ResultsCirc_0016760 and ZBTB7A were upregulated and miR-577 was downregulated in NSCLC tissues and cells. Circ_0016760 exhaustion curbed the colony formation, migration, invasion, and ECAR of NSCLC cells in vitro and impeded tumor growth in vivo. Mechanically, circ_0016760 modulated ZBTB7A expression via sponging miR-577 in NSCLC cells. MiR-577 downregulation abolished the repressive effects of circ_0016760 silencing on colony formation, migration, invasion, and ECAR of NSCLC cells. Also, ZBTB7A upregulation overturned the repressive impacts of miR-577 elevation on colony formation, migration, invasion, and ECAR of NSCLC cells.ConclusionCirc_0016760 silencing impeded NSCLC advancement through regulation of the miR-577/ZBTB7A axis.

Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1.

Objective Nonalcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases. However, the pathogenesis of NAFLD is not still unclear. This study aims at evaluating the role of zinc finger and BTB domain-containing 7A (ZBTB7A) in NAFLD. Methods Western blotting, real-time reverse transcription PCR (RT-PCR), and immunohistochemistry were submitted to evaluate the level of ZBTB7A in the high fatty diet- (HFD-) induced NAFLD mouse model. In vitro, the expression of ZBTB7A was assessed in oleic acid- (OA-) induced HepG2 cells with western blotting and RT-PCR. The luciferase reporter assay was used to estimate the effect of ZBTB7A on the SREBP1 and NF-κB, and the ChIP assay was subjected to evaluate the direct binding to the SREBP1 promoter. Oil Red staining was used to detect lipid accumulation, and the ELISA was used to verify the levels of TG, T-CHO, and MDA. ZBTB7A was knocked down with siRNA, and RT-PCR was performed to analyze the lipogenesis-, fatty acid transporter-, and oxidation metabolism-related genes expression. The levels of ZBTB7A in primary hepatocyte, Kupffer, and hepatic stellate cells (HSCs) were tested by RT-PCR. Results The upregulation of ZBTB7A expression was assessed in NAFLD mice, and ZBTB7A expression was positively correlated with TNFα, IL-6, TG, T-CHO, and MDA. ZBTB7A was highly expressed in the hepatocytes. In vitro, OA-induced ZBTB7A expression and ZBTB7A expression were closely associated with SREBP1c. ZBTB7A could activate the promoter activity of SREBP1 and activate NF-κB activity. Interestingly, the direct binding of ZBTB7A in the SREBP1 promoter was acquired in HepG2 cells. Inhibition of ZBTB7A expression could attenuate OA-induced lipid accumulation, inhibit the expression of the lipogenesis-related genes and fatty acid transporter genes, and promote the expression of oxidation metabolism-related genes. Conclusion ZBTB7A plays a significant role in the development process of NAFLD, and obesity-induced upregulation of ZBTB7A promotes lipid accumulation through activation of SREBP1 and NF-κB. ZBTB7A may be a potential novel target for the therapy of NAFLD.

ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF‑κB signaling pathway.

Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Krüppel erythroid myeloid oncogenic factor, is critical for the tumorigenicity and progression of various cancer types. ZBTB7 has been reported to promote the cell proliferation of colorectal cancers (CRC). However, the function of ZBTB7 to 5-fluorouracil (5‑FU) resistance has not yet been studied. In the current study, ZBTB7 expression and function in 5‑FU resistance in CRC were investigated using with multidisciplinary approaches, including western blot analysis, Transwell assay, CCK8 and a tumor xenograft model. Overexpression of ZBTB7 was increased the level of proteins associated with cell invasion and epithelial-mesenchymal transition. ZBTB7 inhibition attenuated the invasion and enhanced the apoptosis of CRC cells. IC50 values and cell viability were significantly reduced in cells with short hairpin RNA (shRNA)-mediated ZBTB7 depletion compared with the control group. 5‑FU administration decreased viability to a greater extent in the ZBTB7-shRNA group compared with the control, which was dose- and time-dependent. Analysis of gene expression omnibus data demonstrated that ZBTB7 mediated 5‑FU resistance, potentially through nuclear factor (NF)-κB signaling. NF‑κB inhibitor SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings demonstrated that ZBTB7 mediated 5‑FU resistance in CRC cells through NF‑κB signaling. Thus, targeting ZBTB7 and NF‑κB signaling may be an effective strategy to reverse 5‑FU resistance in CRC.

Abstract 479: miR-372 enhances tumorigenesis and drug resistance in oral carcinoma by targeting ZBTB7A transcription factor

Abstract miRNA-mediated post-transcriptional regulation of targeted genes plays crucial roles in neoplastic process. miR-372 has been shown an oncogenic miRNA which is hypoxia-inducible and is conspicuously up-regulated in oral squamous cell carcinoma (OSCC). Zinc finger and BTB domain containing 7A (ZBTB7A) is a transcriptional repressor modulating a great diversities of physiological or oncogenic regulation. This study identified that ZBTB7A was a direct target of miR-372. ZBTB7A was down-regulated in 75% of OSCC tumors relative to adjacent oral mucosa. Reverse correlation across miR-372 expression and ZBTB7A expression was found in tumor samples. In OSCC cells with the stable knockdown of ZBTB7A, the oncogenic potential and drug resistance increased. Whereas, such increase was attenuated by ZBTB7A expression. High throughput screening and validation assay confirmed that ZBTB7A was able to repress multiple oncogenic factors and activate the expression of Trail-R1, Trail-R2 and Fas to increase the drug sensitivity in OSCC cells. miR-372 induction drastically repressed the expression of apoptosis genes by inhibiting ZBTB7A. This was accompany with the enrichment of oncogenicity and the increased tolerance to the toxicity of cisplatin and taxol. This study signifies the importance of miR-372-ZBTB7A-downstream effectors in mediating pathogenesis and drug resistance of OSCC. Interception of this pathogenic cascade would confer therapeutic benefits against oral carcinoma. Citation Format: Li-Yin Yeh, Chung-Hsien Chou, Chung-Ji Liu, Shu-Chun Lin, Kuo-Wei Chang. miR-372 enhances tumorigenesis and drug resistance in oral carcinoma by targeting ZBTB7A transcription factor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 479.

Expression of Zinc Finger and BTB Domain-containing 7A in Colorectal Carcinoma.

Previous studies have revealed that zinc finger and BTB domain-containing 7A (ZBTB7A), an important proto-oncogene, plays multiple roles in carcinogenesis and is up-regulated in several human malignancies. However, the expression of ZBTB7A in colorectal carcinoma (CRC) has seldom been documented. In this study, we investigated the differential expression of ZBTB7A in CRC cell lines and tissues. Expression levels of ZBTB7A mRNA and protein were examined in CRC cell lines. ZBTB7A protein expression was also evaluated in tissue samples of normal colonic mucosa, high-grade dysplasia, and CRC using immunohistochemical staining. All CRC cell lines exhibited significantly higher ZBTB7A mRNA expression levels than did normal colonic epithelial cells. The ZBTB7A protein expression levels were clearly higher in the CRC cell lines than in the normal colonic epithelial cells. Consistent with the cell line data, immunostaining revealed that there were significant differences in ZBTB7A protein expression between tissue samples of CRC and normal colonic mucosa (p=0.048) and high-grade dysplasia (p=0.015). In addition, metastatic CRC exhibited significantly higher ZBTB7A protein expression levels than primary CRC (p=0.027). We demonstrated that ZBTB7A expression is up-regulated in CRC cell lines and tissues. Our data suggest that ZBTB7A is involved in the development and progression of CRC.

Upregulation of ZBTB7A exhibits a tumor suppressive role in gastric cancer cells.

Gastric cancer presents as a complex solid tumor and is the third leading cause of global cancer‑associated mortality. The genetic alterations in gastric cancer remain unclear and deserve further investigation. Mining The Cancer Genome Atlas gastric adenocarcinoma dataset identified a frequent loss of the zinc finger and BTB domain containing7A (ZBTB7A) gene locus and a significant correlation between low ZBTB7A expression and poor patient survival. ZBTB7A belongs to the POZ/BTB and Kruppel transcription factor family. In the present study, overexpression of ZBTB7A in a gastric cancer cell line induced cell cycle arrest at the S phase. Upregulation of ZBTB7A also promoted apoptosis and repressed cell migration. The results of the present study indicated that ZBTB7A functions as a tumor suppressor in gastric cancer cells. Understanding the role of ZBTB7A in gastric cancer may provide important clinical insight for treatment.

The expression and clinical significance of ZBTB7 in transitional cell carcinoma of the bladder.

Zinc finger and BTB domain containing 7A (ZBTB7) is a ZBTB protein family member of transcriptional repressors that serves a critical role in cell transformation and malignancy. However, the association between ZBTB7 expression in bladder cancer tissues and the prognosis of patients remains unclear. The aim of the current study was to detect the expression of ZBTB7 in transitional cell carcinoma (TCC) of the bladder and normal bladder mucous tissues to evaluate the diagnostic and prognostic value of ZBTB7 in TCC of the bladder. A total of 100 TCC specimens were analyzed and the expression of ZBTB7 mRNA was examined via reverse transcription-quantitative polymerase chain reaction. The expression of ZBTB7 protein was examined by western blotting and immunohistochemistry. The association between ZBTB7 expression and the clinical prognosis of patients from the TCGA database was analyzed. High expression of ZBTB7 mRNA and protein in TCC tissue was detected and TCC expression was significantly higher in TCC tissue than in normal bladder mucous tissues (P<0.05). Furthermore, ZBTB7 expression was associated with recurrence, a larger tumor size and higher tumor grade. In terms of overall and recurrence-free survival, the group expressing high levels of ZBTB7 exhibited lower overall and recurrence-free survival compared with the low ZBTB7 expression group, although these differences were not statistically significant. Therefore, ZBTB7 may be important in the initiation and progression of TCC.