Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness

Huang, Chuanqian; Chen, Renli; Zheng, Fang-Jing; Tang, Yirong; Wang, Xiukang; Chen, Zichun; Lai, Xin

doi:10.1186/s12935-021-01828-9

Cited by 11 publications

(10 citation statements)

References 36 publications

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“…ATF3, a key regulator, belongs to the CAMP response element binding protein family with basic leucine zipper structure (BZIP) ( 38 ). ATF3 plays different or even opposite roles in different cellular states by transforming into an isodimer or by combining with other BZIP proteins, which is involved in pathological processes, such as oxidative stress, apoptosis, regulation of Th2 cytokines, and signal transduction ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma

et al. 2022

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Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first proposed that the TL1A/DR3 axis was significantly upregulated in patients and mice with both asthma and high TNF-a expression and in TNF-a-stimulated epithelial Beas-2B cells. Two independent approaches were used to demonstrate that the TL1A/DR3 axis of mice was strongly correlated with TNF-a in terms of exacerbating asthmatic epithelial–mesenchymal transformation (EMT). First, high expression levels of EMT proteins (e.g., collagen I, fibronectin, N-cadherin, and vimentin) and TL1A/DR3 axis were observed when mice airways were stimulated by recombinant mouse TNF-a protein. Moreover, EMT protein and TL1A/DR3 axis expression synchronously decreased after mice with OVA-induced asthma were treated with infliximab by neutralizing TNF-a activity. Furthermore, the OVA-induced EMT of asthmatic mice was remarkably improved upon the deletion of the TL1A/DR3 axis by knocking out the TL1A gene. TL1A siRNA remarkably intervened EMT formation induced by TNF-a in the Beas-2B cells. In addition, EMT was induced by the addition of high concentrations of recombinant human sTL1A with the cell medium. The TL1A overexpression via pc-mTL1A in vitro remarkably increased the EMT formation induced by TNF-a. Overall, these findings indicate that the TL1A/DR3 axis may have a therapeutic role for asthmatic with high TNF-a level.

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Section: Discussionmentioning

confidence: 99%

TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma

et al. 2022

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“…To begin, PAsp[DET-DBCO(- ss -siRNA)&CDM] was incubated in a number of cancerous cells, including SGC-7901, A549, and MCF-7 cells. As shown in Figures S3 and S4, the cellular uptake efficiencies appeared to coincide with the cytomembrane levels of CD44, wherein higher cellular uptake efficiencies were obtained from CD44(+) cells of SGC-7901 and A549 rather than CD44(−) cells of MCF-7 . Moreover, SGC-7901 cells were presaturated with hyaluronan for blocking CD44, followed by addition and incubation with PAsp[DET-DBCO(- ss -siRNA)&CDM].…”

Section: Results and Discussionmentioning

confidence: 92%

“…As shown in Figures S3 and S4, the cellular uptake efficiencies appeared to coincide with the cytomembrane levels of CD44, wherein higher cellular uptake efficiencies were obtained from CD44(+) cells of SGC-7901 and A549 rather than CD44(−) cells of MCF-7. 28 Moreover, SGC-7901 cells were presaturated with hyaluronan for blocking CD44, followed by addition and incubation with PAsp[DET-DBCO-(-ss-siRNA)&CDM]. As shown in Figure 3b, a pronounced drop in cellular uptake of PAsp[DET-DBCO(-ss-siRNA) &CDM] was identified for the cells presaturated from hyaluronan.…”

Section: ■ Results and Discussionmentioning

confidence: 97%

Polymeric RNAi Constructs Tailored with Appreciable Transcellular Trafficking Functions for Potential Suppression of Parathyroid Hormone Production

Mou

Tian

et al. 2021

Bioconjugate Chem.

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Polymeric small interfering RNA (siRNA) conjugate was elaborated to sequentially circumvent the predefined biological barriers encountered in the journey of transcellular delivery of siRNA into cytosol. Herein, classic ring-opening polymerization was employed for synthesis of well-defined poly(amino acid) derivatives possessing an array of carboxyl groups in an attempt to resemble the structural characteristics of hyaluronan. Furthermore, the hyaluronan-like synthetic was conjugated with a multiple of siRNA through a glutathione (GSH)-responsive disulfide linkage. The siRNA conjugate appeared to utilize the hyaluronan-specific receptors of CD44 for cell internalization, indicating similar functionalities to our hyaluronan-mimicking synthetic. Furthermore, the carboxyl groups of hyaluronan-like synthetics were designed to be selectively detached in subcellular acidic endosomes/lysosomes and transform into the cytomembrane-disruptive flanking ethylenediamine moieties, which appeared to be crucial in facilitating translocation of siRNA payloads from entrapment and degradation in lysosomes toward the cytosol. Eventually, active siRNA could be smoothly released from the synthetic due to the GSH cleavage disulfide linkage (disulfide), consequently accounting for potent RNA knockdown activities (>90%) toward cancerous cells. In addition, appreciable knockdown of parathyroid hormone was also achieved from our proposed siRNA conjugates in parathyroid cells. Hence, the elaborated siRNA conjugate showed tremendous potential in treatment of hyperparathyroidism, and could be developed further for systemic RNA interference (RNAi) therapeutics. Moreover, this study could also be the first example of a synthetic mimic to hyaluronan acquiring its functionalities, which could have important implications for further development of biomimic materials in pursuit of biomedical applications.

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“…The main risk factors of gastric cancer include a poor diet, a sedentary lifestyle and Helicobacter pylori infection ( 3 ). Despite recent advancements in treatment strategies, the 5-year survival rate of patients with gastric cancer remains <10%, and metastasis of gastric cancer cells is the main cause of mortality ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression

Zhao

2021

Oncol Lett

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Drug resistance is a key factor affecting the treatment of gastric cancer. The resistance of gastric cancer cells to anticancer drugs, such as cisplatin (DDP), remains a major challenge to patient recovery. The present study aimed to investigate the roles of C-terminal-binding protein 1 (CTBP1) in the DDP resistance of gastric cancer cells and to determine its regulatory effect on DNA repair protein RAD51 homolog 1 (RAD51). The DDP-resistant human gastric cancer AGS and HGC cell lines, AGS/DDP and HGC-27/DDP, respectively, were established and CTBP1 expression was detected by western blotting. In addition, Cell Counting Kit-8, colony formation and flow cytometry assays were performed to detect the proliferation and apoptosis of these two cell lines following CTBP1 knockdown. The expression levels of apoptosis-related proteins were detected by western blotting. In addition, RAD51 was overexpressed in CTBP1 knockdown cells, and proliferation and apoptosis were subsequently determined using the aforementioned methods. The results demonstrated that CTBP1 expression was notably increased in DDP-resistant gastric cancer cells. Furthermore, CTBP1 knockdown suppressed the proliferation and induced the apoptosis of AGS/DDP and HGC-27/DDP cells. Notably, CTBP1 promoted RAD51 expression in DDP-resistant gastric cancer cells. Overexpression of RAD51 in CTBP1 knockdown AGS/DDP and HGC-27/DDP cells rescued the proliferation and alleviated the apoptosis of these cells. Taken together, the results of the present study suggested that CTBP1 may enhance the DDP resistance of gastric cancer cells by activating RAD51 expression, thus providing a potential novel therapy (CTBP1 knockdown) for the clinical treatment of patients with gastric cancer.

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Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness

Cited by 11 publications

References 36 publications

TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma

TL1A/DR3 Axis, A Key Target of TNF-a, Augments the Epithelial–Mesenchymal Transformation of Epithelial Cells in OVA-Induced Asthma

Polymeric RNAi Constructs Tailored with Appreciable Transcellular Trafficking Functions for Potential Suppression of Parathyroid Hormone Production

CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression

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