4‐Phenybutyric acid promotes gastric cancer cell migration via histone deacetylase inhibition‐mediated HER3/HER4 up‐regulation

Shi, Xiaonan; Zheng, Chunlei; Li, Ce; Hou, Kezuo; Wang, Xiaoxun; Yang, Zichang; Liu, Chang; Liu, Yunpeng; Che, Xiaofang; Qu, Xiujuan

doi:10.1002/cbin.10866

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Firstly, the 4-PBA treatment significantly promoted the cell migration in the following 24 h after scratch damage, indicating a stronger self-repairing capability of the IPEC-J2 monolayer enhanced by the 4-PBA. A previous study reported that 4-PBA promotes cell migration of MGC-803 and MGC-823 cell lines via histone deacetylase inhibition ( Shi et al., 2018 ). However, whether the 4-PBA exerts similar effects on histone deacetylase inhibition in the IPEC-J2 cells was unclear, which warrants continual study in our further work.…”

Section: Discussionmentioning

confidence: 99%

4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model

et al. 2021

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As the first line of defence against pathogens and endotoxins crossing the intestine-blood barrier, the intestinal epithelial barrier plays a determinant role in pigs' health and growth. 4-Phenylbutyric acid (4-PBA), an aromatic fatty acid, was reported to benefit homeostasis of endoplasmic reticulum and protein synthesis. However, whether 4-PBA affects intestinal epithelial barrier function in pigs is unknown. This study aimed to explore the effects of 4-PBA on the intestinal barrier function, using in vitro models of well-differentiated intestinal porcine epithelial cell (IPEC-J2) monolayers in the transwell plates. Cell monolayers with or without 4-PBA (1.0 mmol/L) treatment were challenged with physical scratch, deoxynivalenol (DON, 2.0 μg/mL, 48 h), and lipopolysaccharide (LPS, 5.0 μg/mL, 48 h), respectively. Transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD-4) permeability were measured to indicate barrier integrity and permeability. Real-time PCR and Western blot were conducted to determine relative gene and protein expressions of tight junction proteins. As expected, physical scratch, DON, and LPS challenges decreased TEER and increased FD-4 permeability. 4-PBA treatment accelerated cell mitigation and rehabilitation of the physical scratch-damaged intestinal epithelial barrier but did not alleviate DON or LPS induced barrier damage. However, once 48-h DON and LPS challenges were removed, rehabilitation of the epithelial barrier function of IPEC-J2 monolayer was accelerated by the 4-PBA treatment. Also, the relative gene and protein expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 were further upregulated by the 4-PBA treatment during the barrier rehabilitation. Taken together, 4-PBA accelerated the IPEC-J2 cell monolayer barrier recovering from physical scratch, DON-, and LPS-induced damage, via enhancing cell mitigation and expressions of tight junction proteins.

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Section: Discussionmentioning

confidence: 99%

4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model

et al. 2021

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“…This protects EBV from acetylation by NAT1 during lytic replication. ERBB3 has been reported to be involved in mediating the regulations of acetylation and cell apoptosis through its signaling pathway [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating genetic-and-epigenetic networks, and the cellular mechanisms occurring in Epstein–Barr virus-infected human B lymphocytes via big data mining and genome-wide two-sided NGS data identification

Jheng

Chen

2018

PLoS ONE

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Epstein–Barr virus (EBV), also known as human herpesvirus 4, is prevalent in all human populations. EBV mainly infects human B lymphocytes and epithelial cells, and is therefore associated with their various malignancies. To unravel the cellular mechanisms during the infection, we constructed interspecies networks to investigate the molecular cross-talk mechanisms between human B cells and EBV at the first (0–24 hours) and second (8–72 hours) stages of EBV infection. We first constructed a candidate genome-wide interspecies genetic-and-epigenetic network (the candidate GIGEN) by big database mining. We then pruned false positives in the candidate GIGEN to obtain the real GIGENs at the first and second infection stages in the lytic phase by their corresponding next-generation sequencing data through dynamic interaction models, the system identification approach, and the system order detection method. The real GIGENs are very complex and comprise protein–protein interaction networks, gene/microRNA (miRNA)/long non-coding RNA regulation networks, and host–virus cross-talk networks. To understand the molecular cross-talk mechanisms underlying EBV infection, we extracted the core GIGENs including host–virus core networks and host–virus core pathways from the real GIGENs using the principal network projection method. According to the results, we found that the activities of epigenetics-associated human proteins or genes were initially inhibited by viral proteins and miRNAs, and human immune responses were then dysregulated by epigenetic modification. We suggested that EBV exploits viral proteins and miRNAs, such as EBNA1, BPLF1, BALF3, BVRF1 and miR-BART14, to develop its defensive mechanism to defeat multiple immune attacks by the human immune system, promotes virion production, and facilitates the transportation of viral particles by activating the human genes NRP1 and CLIC5. Ultimately, we propose a therapeutic intervention comprising thymoquinone, valpromide, and zebularine to act as inhibitors of EBV-associated malignancies.

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“…The protein from cells and exosomes were detected by Western blot, performed as previously described (23). The target bands of proteins were detected with an enhanced chemiluminescence reagent (SuperSignal Western Pico Chemiluminescent Substrate, Pierce; Thermo Fisher Scientific, Inc.) and were scanned by the Electrophoresis Gel Imaging Analysis System (DNR Bio-Imaging Systems, Neve Yamin, Israel) and analyzed by NIH Image J software.…”

Section: Western Blotmentioning

confidence: 99%

“…The isolation of total RNA was performed as previously described (23). For microRNAs, The One Step PrimeScript R miRNA cDNA Synthesis Kit (Takara, Japan) was used for RNA reverse transcription.…”

Section: Rna Isolation and Reverse Transcription-quantitative Real-time Pcrmentioning

confidence: 99%

5-FU-Induced Upregulation of Exosomal PD-L1 Causes Immunosuppression in Advanced Gastric Cancer Patients

et al. 2020

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Although the cytotoxic chemotherapeutic agent 5-fluorouracil (5-FU) is generally considered to directly kill cancer cells and exert immunostimulatory effects in advanced gastric cancer, accumulating evidence indicates that it upregulates the expression of PD-L1, a representative immune checkpoint blockade molecule involved in negative regulation of the immune response. It was reported that exosomes could transfer functional PD-L1 locally and distantly to suppress the antitumor immune response. However, whether 5-FU alters the expression of exosomal PD-L1 and induces immunosuppression in gastric cancer remains unclear. Herein, we found that 5-FU increased gastric cancer-derived exosomal PD-L1. Importantly, compared with baseline levels, circulating exosomal PD-L1 was significantly upregulated in 21 stage III-IV gastric cancer patients after two, four, and six repeated cycles of fluoropyrimidine treatment (P = 0.009, P = 0.047, and P = 0.023, respectively), accompanied by decreased amounts of IFN-γ, TNF-α, IL-2, IL-6, and GM-CSF (P = 0.014, P = 0.004, P = 0.009, P = 0.031, and P = 0.014, respectively). Additionally, circulating exosomal PD-L1 was increased more significantly in clinical non-responders compared with responders (P = 0.018). Furthermore, exosomal PD-L1 induced apoptosis in Jurkat T cells and inhibited T cell activation in PBMCs, which could be partly reversed by nivolumab. These results suggested that 5-FU-induced upregulation of exosomal PD-L1 causes systemic immunosuppression in advanced gastric cancer following multiple cycles of chemotherapy, especially after two cycles.

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4‐Phenybutyric acid promotes gastric cancer cell migration via histone deacetylase inhibition‐mediated HER3/HER4 up‐regulation

Cited by 11 publications

References 30 publications

4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model

4-Phenylbutyric acid accelerates rehabilitation of barrier function in IPEC-J2 cell monolayer model

Investigating genetic-and-epigenetic networks, and the cellular mechanisms occurring in Epstein–Barr virus-infected human B lymphocytes via big data mining and genome-wide two-sided NGS data identification

5-FU-Induced Upregulation of Exosomal PD-L1 Causes Immunosuppression in Advanced Gastric Cancer Patients

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