Identification of PGRMC1 as a Candidate Oncogene for Head and Neck Cancers and Its Involvement in Metabolic Activities

Zhao, Yue; Ruan, Xiangyan

doi:10.3389/fbioe.2019.00438

Cited by 20 publications

(15 citation statements)

References 33 publications

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“…One example is the role of Pgrmc1 in breast cancer [ 32 , 33 ], as Pgrmc1 has been recently identified to play important roles in the survival duration and metastasis of breast cancers in a murine PyMT model [ 34 ]. Pgrmc1 is also known to be highly expressed in various types of cancers and associated with the survival rate of patients with head and neck cancer [ 35 ], lung and ovarian cancers [ 36 ], and breast cancer [ 32 , 33 ]. Of note, PGRMC1 exists in protein complexes including EGFR and modulates its expression levels in multiple cancer cell lines (breast, lung, colon cancers) and affects their proliferation and chemoresistance [ 20 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses

Lee

Heo

et al. 2021

Cancers

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Pgrmc1 is a non-canonical progesterone receptor related to the lethality of various types of cancer. PGRMC1 has been reported to exist in co-precipitated protein complexes with epidermal growth factor receptor (EGFR), which is considered a useful therapeutic target in hepatocellular carcinoma (HCC). Here, we investigated whether Pgrmc1 is involved in HCC progression. In clinical datasets, PGRMC1 transcription level was positively correlated with EGFR levels; importantly, PGRMC1 level was inversely correlated with the survival duration of HCC patients. In a diethylnitrosamine (DEN)-induced murine model of HCC, the global ablation of Pgrmc1 suppressed the development of HCC and prolonged the survival of HCC-bearing mice. We further found that increases in hepatocyte death and suppression of compensatory proliferation in the livers of DEN-injured Pgrmc1-null mice were concomitant with decreases in nuclear factor κB (NF-κB)-dependent production of interleukin-6 (IL-6). Indeed, silencing of Pgrmc1 in murine macrophages led to reductions in NF-κB activity and IL-6 production. We found that the anti-proinflammatory effect of Pgrmc1 loss was mediated by reductions in EGFR level and its effect was not observed after exposure of the EGFR inhibitor erlotinib. This study reveals a novel cooperative role of Pgrmc1 in supporting the EGFR-mediated development of hepatocellular carcinoma, implying that pharmacological suppression of Pgrmc1 may be a useful strategy in HCC treatment.

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Section: Introductionmentioning

confidence: 99%

Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses

Lee

Heo

et al. 2021

Cancers

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“…The aberrant expression of PGRMC1 at both transcript and protein levels have been reported in multiple types of cancer, including breast (Neubauer et al, 2013;Li et al, 2019), ovarian (Peluso et al, 2008;Mir et al, 2012), as well as head and neck cancer (Zhao and Ruan, 2019). PGRMC1 may regulate the proliferation and progression of breast cancer cells, potentially by altering lipid metabolism and by activating key oncogenic signaling pathways, such as ERα expression and activation, as well as EGFR signaling (Asperger et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Implication of PGRMC1 in Triple-Negative Breast Cancer

Ruan

Zhang

et al. 2021

Front. Bioeng. Biotechnol.

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TNBC represents the most malignant subtype of breast cancer with heterogenicity and poor prognosis. PGRMC1 has been reported to predict worse prognosis and correlate with MHT mediated signal transduction in breast cancer, whereas its involvement in TNBC remains poorly explored. The purpose of the study was to explore the roles of PGRMC1 in TNBC. Bioinformatic approaches were performed to analyzed the expression of PGRMC1 among different subtypes of breast cancers using RNA-seq data from the TCGA, METABRIC and GEO databases. PGRMC1 mRNA expression and survival in breast cancer were analyzed. Furthermore, we analyzed the expression of PGRMC1 in TNBC by single cell RNA-seq data and immunohistochemistry. The expression of PGRMC1 in TNBC group was significantly higher compared with that of Luminal subtypes, especially in the epithelia cells, which was further proved by IHC at protein level. Better overall survival (p = 0.027) was observed in the patients with lower expression of PGRMC1. Different states of hormone and Her2 receptors contributed to the distinct functions of PGRMC1. In TNBC, PGRMC1 might play an important role in mitochondrial functions. In summary, this study revealed the correlation between PGRMC1 expression and its clinical significance in TNBC, probably through mitochondria-associated pathway, which may provide new ideas for prognosis and therapy of TNBC.

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“…Therefore, ARF4 may play key roles in HO development. PGRMC1/Sigma-2 receptor is confirmed to play key roles in the function of tumor proliferation (such as breast tumors, lung adenocarcinoma cells, and ovarian cancer) and chemoresistance (44)(45)(46)(47). Recent research showed that PGRMC1 significantly suppresses the hydrogen peroxide-induced oxidative stress response in full-thickness fetal membrane explants and chorion cells (48).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Biomarkers and Pathological Process of Heterotopic Ossification: Weighted Gene Co-Expression Network Analysis

et al. 2020

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Heterotopic ossification (HO) is the formation of abnormal mature lamellar bone in extra-skeletal sites, including soft tissues and joints, which result in high rates of disability. The understanding of the mechanism of HO is insufficient. The aim of this study was to explore biomarkers and pathological processes in HO+ samples. The gene expression profile GSE94683 was downloaded from the Gene Expression Omnibus database. Sixteen samples from nine HO- and seven HO+ subjects were analyzed. After data preprocessing, 3,529 genes were obtained for weighted gene co-expression network analysis. Highly correlated genes were divided into 13 modules. Finally, the cyan and purple modules were selected for further study. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment indicated that the cyan module was enriched in a variety of components, including protein binding, membrane, nucleoplasm, cytosol, poly(A) RNA binding, biosynthesis of antibiotics, carbon metabolism, endocytosis, citrate cycle, and metabolic pathways. In addition, the purple module was enriched in cytosol, mitochondrion, protein binding, structural constituent of ribosome, rRNA processing, oxidative phosphorylation, ribosome, and non-alcoholic fatty liver disease. Finally, 10 hub genes in the cyan module [actin related protein 3 (ACTR3), ADP ribosylation factor 4 (ARF4), progesterone receptor membrane component 1 (PGRMC1), ribosomal protein S23 (RPS23), mannose-6-phosphate receptor (M6PR), WD repeat domain 12 (WDR12), synaptosome associated protein 23 (SNAP23), actin related protein 2 (ACTR2), siah E3 ubiquitin protein ligase 1 (SIAH1), and glomulin (GLMN)] and 2 hub genes in the purple module [proteasome 20S subunit alpha 3 (PSMA3) and ribosomal protein S27 like (RPS27L)] were identified. Hub genes were validated through quantitative real-time polymerase chain reaction. In summary, 12 hub genes were identified in two modules that were associated with HO. These hub genes could provide new biomarkers, therapeutic ideas, and targets in HO.

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Identification of PGRMC1 as a Candidate Oncogene for Head and Neck Cancers and Its Involvement in Metabolic Activities

Cited by 20 publications

References 33 publications

Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses

Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses

Comprehensive Analysis of the Implication of PGRMC1 in Triple-Negative Breast Cancer

Identification of the Biomarkers and Pathological Process of Heterotopic Ossification: Weighted Gene Co-Expression Network Analysis

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