The Interplay between Glucose-Regulated Protein 78 (GRP78) and Steroids in the Reproductive System

Hebert-Schuster, Marylise; Rotta, Belinda Elisabeth; Kirkpatrick, Brenna J; Gadrey, Jean; Cohen, Marie

doi:10.3390/ijms19071842

Cited by 18 publications

(11 citation statements)

References 57 publications

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“…GRP78, the key protein in the ER, is implicated in various diseases, such as tumors and neurodegenerative diseases ( Hebert-Schuster et al, 2018 ; Casas, 2017 ). In the current study, we found that GRP78 was highly expressed in lung adenocarcinoma and lung squamous cell carcinoma, and was associated with a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Lian

2020

Biology Open

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This study aimed to investigate the pathophysiological role of GRP78 in the survival of lung cancer cells. Lung cancer patient data from public databases were used to analyze the expression of GRP78 and its influence on prognoses. In vivo, GRP78 protein expression was analyzed in an established urethane-induced lung tumor mouse model. In vitro, the effects of targeted inhibition of GRP78 by HA15 in lung cancer cells were assessed, with cell viability analyzed using a CCK-8 assay, cell proliferation using an EdU assay, apoptosis and cell cycle using flow cytometry, subcellular structure using electron microscopy, and relative mRNA and protein expression using RT-PCR, western blotting or immunofluorescence assay. The results showed that GRP78 was highly expressed in the lung tissue of lung cancer mice model or patients, and was associated with a poor prognosis. After inhibition of GRP78 in lung cancer cells by HA15, cell viability was decreased in a dose- and time-dependent manner, proliferation was suppressed and apoptosis promoted. Unfolded protein response signaling pathway proteins were activated, and the autophagy-related proteins and mRNAs were upregulated. Therefore, targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy.

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Section: Discussionmentioning

confidence: 99%

Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Lian

2020

Biology Open

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“…GRP78 further mediates endocytosis into lysosomes of liver cancer cells, and ferritin lysis releases adriamycin under acidic environment, so as to kill liver cancer cells ( Table 1) (19,20). In addition, GRP78 level on the surface of cancer cells has been found in prostate cancer studies to be related to tumor stage, and the level of anti-GRP78 antibody is parallel to the concentration of tumor-specific antigen in serum (27,37,38), which further suggests the effect of GRP78 on driving tumor progression. Therefore, the expression of GRP78 can be considered as a promoter of many cancer characteristics, and it has been proved that it is up-regulated not only in a variety of tumor cells, but also in tumor-related macrophages.…”

Section: New Targets For Tumor Therapymentioning

confidence: 99%

Targeting the GRP78 Pathway for Cancer Therapy

Luo

Zhu

2020

Front. Med.

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The 78-kDa glucose-regulated protein (GRP78) plays an important part in maintaining protein stability, regulating protein folding, and inducing apoptosis autophagy, which is considered as a powerful protein. Meanwhile, it also plays a role in ensuring the normal function of organs. In recent years, more and more researches have been carried out on the targeted therapy of GRP78, mainly focusing on its relevant role in tumor and its role as a major modulator and modulator of subordinate pathways. The ability of GRP78 to respond to endoplasmic reticulum stress (ERS) determines whether tumor cells survive and whether the changes in expression level of GRP78 regulated by endoplasmic reticulum (ER) caused by various factors will directly or indirectly affect cell proliferation, apoptosis, and injury, or reduce the body's defense ability, or have protective effects on various organs.

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“…6). During the synthesis of E 2 , StAR can transport cholesterol from the outer to the inner mitochondrial membrane, where it is converted to pregnenolone by CYP11A1 [41]. Aromatase (CYP19A1) in GCs transforms testosterone into estradiol [41,42].…”

Section: Discussionmentioning

confidence: 99%

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

Shi

Zhou

et al. 2020

J Animal Sci Biotechnol

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Background Granulosa cells (GCs) proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on GCs are unclear. This study focuses on miR-214-3p in terms of the effects on GCs proliferation and estradiol synthesis. Results Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine GCs. MiR-214-3p can increase the percentage of S-phase cells, the number of EdU labeled positive cells, and cell viability. However, E2 concentration was reduced after miR-214-3p agomir treatment. We also found that miR-214-3p up-regulates the expression of cell cycle genes including cell cycle protein B (Cyclin B), cell cycle protein D (Cyclin D), cell cycle protein E (Cyclin E), and cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, but down-regulates the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis are Mfn2 and NR5A1, respectively. Conclusions Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine GCs and therefore may be a target gene for regulating follicular development.

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The Interplay between Glucose-Regulated Protein 78 (GRP78) and Steroids in the Reproductive System

Cited by 18 publications

References 57 publications

Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Targeting the GRP78 Pathway for Cancer Therapy

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

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