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

Sun, Guang; Peng, Bo; Xie, Quan; Ruan, Jianwen; Liang, Xiaofeng

doi:10.3892/mmr.2017.8104

Cited by 13 publications

(12 citation statements)

References 31 publications

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“…Furthermore, mRNA levels of ZBTB7A were examined in these cell lines, and the results of the mRNA levels were in agreement with the protein expression of ZBTB7A. Taken together, these results suggest that ZBTB7A was overexpressed in the liver cancer cells, which was consistent with that reported in the nonsmall-cell lung carcinoma [25], and it was contrasted with prostate cancer, melanoma, triple-negative breast cancer, and gastric cancer [26][27][28][29].…”

Section: Oleic Acid-induced Zbtb7a Expression and Lipid Accumulationsupporting

confidence: 84%

Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1

Zhou

Ren

et al. 2020

BioMed Research International

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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.

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Section: Oleic Acid-induced Zbtb7a Expression and Lipid Accumulationsupporting

confidence: 84%

Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1

Zhou

Ren

et al. 2020

BioMed Research International

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“…It has been reported that TRAIL-R2 selective ligands are superior to TRAIL-R1 selective ligands when triggering apoptosis in colorectal and pancreatic cancer cells (52). Recent studies have shown that ZBTB7A modulates apoptosis and chemosensitivity via a range of different mechanisms across diverse malignancies (24,53). The present study has identified a new function of ZBTB7A, namely the activation TRAIL-R2, which then results in a triggering of apoptosis in OSCC.…”

Section: Discussionmentioning

confidence: 52%

“…However, studies also found that ZBTB7A may also interact with and repress SOX9 (sex determining region Y-box 9), various glycolytic transcription factors and a number of other targets; these findings reveal this protein's functional complexity when mediating tumor suppression (16,17,(19)(20)(21)(22). Although the roles of ZBTB7A in carcinogenesis are controversial and the mechanisms by which it acts remain largely obscure, frequent deletion and downregulation of ZBTB7A has been shown to occur in a range of malignancies including OSCC (20,(23)(24)(25). In addition, miR-106b and other miRNAs have been shown to target ZBTB7A in such malignancies (25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 96%

The miR-372-ZBTB7A Oncogenic Axis Suppresses TRAIL-R2 Associated Drug Sensitivity in Oral Carcinoma

Yeh¹,

Yang

Wu³

et al. 2020

Front. Oncol.

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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.

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“…ZBTB7A acts as a tumor suppressor by repressing the expression of key genes in tumor glycolysis [26] and negatively regulating TGF-β pathway [27]. Previous studies have revealed its tumor suppressor role in a wide variety of cancers [28][29][30]. Again, this is in line with the tumor suppressive function of the TSGs regulated by ZBTB7A.…”

Section: Master Transcriptional Regulators (Mtrs) Of Tsgsmentioning

confidence: 65%

Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues

Sun

Uddin

et al. 2020

Journal of Oncology

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Cancer prevails in various gastrointestinal (GI) organs, such as esophagus, stomach, and colon. However, the small intestine has an extremely low cancer risk. It is interesting to investigate the molecular cues that could explain the significant difference in cancer incidence rates among different GI tissues. Using several large-scale normal and cancer tissue genomics datasets, we compared the gene expression profiling between small intestine and other GI tissues and between GI cancers and normal tissues. We identified 17 tumor suppressor genes (TSGs) which showed significantly higher expression levels in small intestine than in other GI tissues and significantly lower expression levels in GI cancers than in normal tissues. These TSGs were mainly involved in metabolism, immune, and cell growth signaling-associated pathways. Many TSGs had a positive expression correlation with survival prognosis in various cancers, confirming their tumor suppressive function. We demonstrated that the downregulation of many TSGs was associated with their hypermethylation in cancer. Moreover, we showed that the expression of many TSGs inversely correlated with tumor purity and positively correlated with antitumor immune response in various cancers, suggesting that these TSGs may exert their tumor suppressive function by promoting antitumor immunity. Furthermore, we identified a transcriptional regulatory network of the TSGs and their master transcriptional regulators (MTRs). Many of MTRs have been recognized as tumor suppressors, such as HNF4A, ZBTB7A, p53, and RUNX3. The TSGs could provide new molecular cues associated with tumorigenesis and tumor development and have potential clinical implications for cancer diagnosis, prognosis, and treatment.

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

Cited by 13 publications

References 31 publications

Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1

Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1

The miR-372-ZBTB7A Oncogenic Axis Suppresses TRAIL-R2 Associated Drug Sensitivity in Oral Carcinoma

Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues

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