Roles of Zinc Finger Protein 423 in Proliferation and Invasion of Cholangiocarcinoma through Oxidative Stress

Chaiprasert, Timpika; Armartmuntree, Napat; Techasen, Anchalee; Sakonsinsiri, Chadamas; Pinlaor, Somchai; Ungarreevittaya, Piti; Khuntikeo, Narong; Namwat, Nisana; Thanan, Raynoo

doi:10.3390/biom9070263

Cited by 14 publications

(7 citation statements)

References 44 publications

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“…These findings are consistent with previous studies on XB130 in a variety of cancers, e.g., thyroid tumor [19,31], prostate cancer [15], lung cancer [17], gastric cancer [32], breast cancer PLOS ONE [33], colorectal cancer [34], hepatocellular carcinoma [35], and skin tumor [24]. XB130 has been suggested to play significant roles in cancer progression through PI3K/Akt signaling pathway, leading to an increase in tumorigenic properties, including cell growth, migration, invasion and epithelial-mesenchymal transition (EMT) process [17,31,[35][36][37].…”

Section: Discussionsupporting

confidence: 93%

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Section: Discussionsupporting

confidence: 93%

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“…EBF1 is a tumor suppressor in leukemia 10 , breast cancer 11 and cholangiocarcinoma (CCA) 12 . EBF1 suppression is mediated via different mechanisms such as genomic loss in breast cancer 11 , point mutation in pancreatic ductal adenocarcinoma 13 , overexpression of EBF1 inhibitors (ZNF423 and ZNF521) in many cancers, such as CCA 14 , acute lymphoblastic leukemia 15 and nasopharyngeal carcinoma 16 , and aberrant expression of microRNAs targeting EBF1 in white adipose tissues 17 . However, little is known about the importance of epigenetic changes in suppression of EBF1 expression.…”

Section: Introductionmentioning

confidence: 99%

Promoter hypermethylation of early B cell factor 1 (EBF1) is associated with cholangiocarcinoma progression

Armartmuntree¹,

Jusakul²,

Sakonsinsiri³

et al. 2021

J. Cancer

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DNA hypermethylation in a promoter region causes gene silencing via epigenetic changes. We have previously reported that early B cell factor 1 (EBF1) was down-regulated in cholangiocarcinoma (CCA) tissues and related to tumor progression. Thus, we hypothesized that the DNA hypermethylation of EBF1 promoter would suppress EBF1 expression in CCA and induce its progression. In this study, the DNA methylation status of EBF1 and mRNA expression levels were analyzed in CCA and normal bile duct (NBD) tissues using a publicly available database of genome-wide association data. The results showed that the DNA methylation of EBF1 promoter region was significantly increased in CCA tissues compared with those of NBD. The degree of methylation was negatively correlated with EBF1 mRNA expression levels. Using methylation-specific PCR technique, the DNA methylation rates of EBF1 promoter region were investigated in CCA tissues (n=72). CCA patients with high methylation rates of EBF1 promoter region in the tumor tissues (54/72) had a poor prognosis. Higher methylation rates of EBF1 promoter region have shown in all CCA cell lines than that of an immortal cholangiocyte cell line (MMNK1). Upon treatment with the DNA methyltransferase inhibitor 5-Aza-dC, increased EBF1 expression levels and reduced DNA methylation rates were observed in CCA cells. Moreover, restoration of EBF1 expression in CCA cells led to inhibition of cell growth, migration and invasion. In addition, RNA sequencing analysis suggested that EBF1 is involved in suppression of numerous pathways in cancer. Taken together, DNA hypermethylation in the EBF1 promoter region suppresses EBF1 expression and induces CCA progression with aggressive clinical outcomes.

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“…ZNF423, which is required for cerebellar development 26 – 28 , is involved in the development of B lymphoblastic leukemia 29 , 30 . Silencing of ZNF423 has been reported to significantly inhibit cell proliferation and invasion of the cholangiocarcinoma cell line 31 . However, it is unclear whether ZNF423 can be used as an RBP to activate autophagy in PASMCs through posttranscriptional regulatory mechanisms.…”

Section: Introductionmentioning

confidence: 99%

BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs

Wei

Zhang

et al. 2020

Cell Death Dis

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Abnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich elements in the BCAT1 mRNA 3′-untranslated region. Overall, our results identify BCAT1 as a potential therapeutic target for the clinical treatment of lung diseases and reveal a novel posttranscriptional regulatory mechanism and signaling pathway in hypoxia-induced PASMC autophagy.

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Roles of Zinc Finger Protein 423 in Proliferation and Invasion of Cholangiocarcinoma through Oxidative Stress

Cited by 14 publications

References 44 publications

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Promoter hypermethylation of early B cell factor 1 (EBF1) is associated with cholangiocarcinoma progression

BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs

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