ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma

Otsuka, Ryota; Akutsu, Yasunori; Sakata, Haruhito; Hanari, Naoyuki; Murakami, Kentaro; Kano, Masayuki; Takahashi, Masahīko; Matsumoto, Yasunori; Sekino, Nobufumi; Yokoyama, Masaya; Iida, Kei; Matsubara, Hisahiro

doi:10.1159/000476068

Cited by 15 publications

(14 citation statements)

References 28 publications

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“…Zinc Finger Protein 750 (ZNF750), as a transcription factor belonging to one of the Zinc Finger Protein family members, was the top-ranked hypomethylated gene in the dataset. Previous findings revealed that ZNF750 serves as a tumor repressor in oral squamous cell carcinoma 6 and esophageal squamous cell carcinoma 7 . However, the mechanism by ZNF750 governs tumorigenesis and the role of ZNF750 in NPC remain largely unknown.…”

Section: Introductionmentioning

confidence: 97%

m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression

Zhang

Liu

et al. 2018

Cell Death Dis

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Nasopharyngeal carcinoma (NPC) progression is regulated by genetic, epigenetic, and epitranscript modulation. As one of the epitranscript modifications, the role of N6-Methyladenosine (m6A) has not been elucidated in NPC. In the present study, we found that the poorly methylated gene ZNF750 (encoding zinc finger protein 750) was downregulated in NPC tumor tissues and cell lines. Ectopic expression of ZNF750 blocked NPC growth in vitro and in vivo. Further studies revealed that m6A modifications maintained the low expression level of ZNF750 in NPC. Chromatin immunoprecipitation sequencing identified that ZNF750 directly regulated FGF14 (encoding fibroblast growth factor 14), ablation of which reversed ZNF750’s tumor repressor effect. Moreover, the ZNF750-FGF14 signaling axis inhibited NPC growth by promoting cell apoptosis. These findings uncovered the critical role of m6A in NPC, and stressed the regulatory function of the ZNF750-FGF14 signaling axis in modulating NPC progression, which provides theoretical guidance for the clinical treatment of NPC.

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Section: Introductionmentioning

confidence: 97%

m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression

Zhang

Liu

et al. 2018

Cell Death Dis

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“…In other words, ZNF750 is associated with KLF4, a tumor suppressor gene, and is considered to have an important role in treatment resistance. Indeed, we previously revealed that a low ZNF750 expression was associated with poor sensitivity to chemoradiotherapy [11]. In addition, Hu et al [30] revealed that the upregulation of KLF4 by methylseleninic acid could inhibit cell growth in ESCC cells.…”

Section: Discussionmentioning

confidence: 94%

“…ZNF750 was reported to act as a transcriptional regulator of epidermal differentiation, and the expression of ZNF750 induces epidermal differentiation genes and suppresses epidermal progenitor genes [9]. ZNF750 has been shown to function as a tumor suppressor [5,6,10], and we previously reported the relationship between ZNF750 expression and chemoradiotherapy response in ESCC patients [11]. We, therefore, consider ZNF750 to be a notable gene in the field of ESCC.…”

Section: Introductionmentioning

confidence: 96%

ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma

Otsuka

Akutsu²,

Sakata³

et al. 2017

Oncology

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Objective: ZNF750, a transcriptional regulator of epidermal differentiation, has been identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the clinical and prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750 knockdown on cell proliferation, migration, and invasion in ESCC. Methods: A total of 124 patients with ESCC who underwent curative esophagectomy were evaluated in this study. The expression of ZNF750 in surgical specimens was immunohistochemically assessed and used in the analysis of clinicopathological features and overall survival (OS). The molecular role of ZNF750 was investigated by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines. Results: Low ZNF750 expression had a significant correlation with positive lymph node metastasis (p = 0.028). Furthermore, there was a significant relationship between low expression of ZNF750 in ESCC and a poor OS, and a multivariate analysis showed that low ZNF750 expression was an independent prognostic factor (p = 0.020). The cell growth, migration, and invasion were significantly increased by downregulation of ZNF750. Conclusions: The low expression of ZNF750 was significantly associated with a poor prognosis, and ZNF750 expression may, therefore, be a reliable prognostic biomarker in ESCC.

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“…Moreover, high levels of ZNF750 are associated with a good response to chemoradiotherapy, suggesting that ZNF750 could serve as a novel candidate biomarker for chemoradiotherapy sensitivity. 75 …”

Section: Role Of Znfs In Diseasesmentioning

confidence: 99%

Zinc-finger proteins in health and disease

et al. 2017

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Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes. The aim of this review is to provide a comprehensive summary of the current state of knowledge of this class of proteins. Firstly, we describe the actual classification of ZNFs, their structure and functions. Secondly, we focus on the biological role of ZNFs in the development of organisms under normal physiological and pathological conditions.

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ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma

Cited by 15 publications

References 28 publications

m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression

m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression

ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma

Zinc-finger proteins in health and disease

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