GRP78 in lung cancer

Xia, Shengkai; Duan, Wenzhe; Liu, Wenwen; Zhang, Xinri; Wang, Qi

doi:10.1186/s12967-021-02786-6

Cited by 59 publications

(48 citation statements)

References 130 publications

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“…GRP78 plays an important role in the antiapoptotic mechanisms of cancer cells [ 14 ]. Several studies have proven that GRP78 expression positively correlates with tumor development in renal cell carcinoma [ 15 ], lung cancer [ 16 ], and ovarian cancer [ 17 ]. Our data supported that Hotair upregulates GRP78 via hsa-miR-30a-5p, and downregulation of Hotair also inhibited cell proliferation and promoted apoptosis in LSCC.…”

Section: Resultsmentioning

confidence: 99%

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Yuan

Shen

2022

Journal of Immunology Research

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Homeobox (HOX) transcript antisense RNA (Hotair) is elevated in many cancers significantly. However, the oncogenic role of Hotair in human laryngeal squamous cell carcinoma (LSCC) is still unknown. Thus, we explored the expression profile of Hotair and its function in LSCC. We observed high expression levels of Hotair in six LSCC cell lines compared to the human nasopharyngeal epithelial cell line. Knockdown of Hotair inhibited proliferation and enhanced apoptosis of Tu212 and Hep-2 cell lines in vitro. Moreover, the overexpression of hsa-miR-30a-5p inhibited the expression of GRP78 and PD-L1, but Hotair overexpression in LSCC cells rescues both proteins. Furthermore, the impacts of hsa-miR-30a-5p upregulation on the apoptosis and proliferation of LSCC cells were rescued by overexpression of Hotair. Finally, we combined si-Hotair and a VEGF inhibitor to treat LSCC cells in vitro or in vivo and surprisingly observed a significant inhibition of LSCC growth. In summary, these results indicate that Hotair displays an oncogenic role in both malignancy and immune escape in LSCC related to hsa-miR-30a-5p/GRP78/PD-L1 signaling. Therefore, Hotair may be a potential target for treating LSCC.

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Section: Resultsmentioning

confidence: 99%

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Yuan

Shen

2022

Journal of Immunology Research

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“…Previous studies have reported that BiP is involved in the regulation of tumor function, including epithelial–mesenchymal transition (EMT) change, migration, invasion, and tumor-associated angiogenesis, and that VEGF is a downstream regulator of BiP participating in these pathological processes [ 45 – 47 ]. Therefore, the effect of CSC on the expression of VEGF and malignant behaviors were evaluated in YD38 and SCC25 cells after treatment with 120 μg/ml CSC for 48 h. We found that CSC increased the expression of VEGF in OSCC cells, and that the levels of secreted VEGF were significantly higher in the CM collected from OSCC cells incubated with CSC compared to those from the control cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression

et al. 2021

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Background Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. Methods The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. Results Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3′untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3′UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. Conclusions These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

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“…Furthermore, it was shown that the GRP78 level is regulated either directly or indirectly by ATF4 [19]. Phosphorylation of eukaryotic initiation factor-2α (eIF2α) activates ATF4, which regulates the UPR by controlling the expression of UPR target genes that are linked to endoplasmic-reticulum-associated protein degradation (ERAD) and pro-apoptotic CCAAT/enhancer-binding protein (C/ EBP)-homologous protein (CHOP) [19]. In addition, a conserved binding site (5′-TGA CGT GA-3′) for ATF4 is located upstream to the ER stress response element (ERSE) in the mammalian GRP78 promoter.…”

Section: Atf4 As Er Stress Modulator In the Cross-talk With Oxidative...mentioning

confidence: 99%

Mini review ATF4 and GRP78 as novel molecular targets in ER-Stress modulation for critical COVID-19 patients

et al. 2022

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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 4.4 million deaths worldwide as of August 24, 2021. Viral infections such as SARS-CoV2 are associated with endoplasmic reticulum (ER) stress and also increased the level of reactive oxygen species. Activating transcription factor 4 (ATF4) is preferentially translated under integrated stress conditions and controls the genes involved in protein homeostasis, amino acid transport and metabolism, and also protection from oxidative stress. The GRP78, regulated either directly or indirectly by ATF4, is an essential chaperone in the ER and overexpressed and appears on the surface of almost all cells during stress and function as a SARS-CoV2 receptor. In this mini-review article, we briefly discuss the effects of SARS-CoV2 infection on the ER stress, and then the stress modulator functions of ATF4 and GRP78 as novel therapeutic targets were highlighted. Finally, the effects of GRP78 inhibitory components as potential factors for targeted therapies for COVID-19 critical cases were discussed. Keywords COVID-19 disease • ER stress modulation • ATF4 • GRP78 targeting COVID-19 infection and ER stressThe SARS-CoV-2 is a member of Coronaviridae, a kind of enveloped viruses with positive-sense, single-stranded RNA [1]. This virus caused more than 4.4 million deaths worldwide up to August 2021. No specific therapeutic treatment for COVID-19 has been approved so far which highlighting the urgent need to identify new antiviral strategies.

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GRP78 in lung cancer

Cited by 59 publications

References 130 publications

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression

Mini review ATF4 and GRP78 as novel molecular targets in ER-Stress modulation for critical COVID-19 patients

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