Parathyroid hormone‐like hormone plays a dual role in neuroblastoma depending on <scp>PTH</scp>1R expression

García, Marta; Rodríguez-Hernández, Carlos J.; Perez-Jaume, Sara; Goncalves-Alves, Eliana; Lavarino, Cinzia; Mora, Jaume; Torres, Carmen de

doi:10.1002/1878-0261.12542

Cited by 8 publications

(8 citation statements)

References 48 publications

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“…Recently, the structure and dynamics of the active PTH1R have been shown by cryo-electron microscopy (55). Studies from different research groups have reported that the decreased expression of PTH1R was a poor prognosis factor in multiple types of cancer (56)(57)(58)(59). Although PTH1R was found to be highly expressed in normal kidney samples (Figure 5 and Figure S4), the detailed mechanism of PTH1R in renal function and ccRCC has yet to be fully elucidated and requires further study.…”

Section: Metabolic Shift In Clear Cell Renal Cell Carcinomamentioning

confidence: 99%

Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

et al. 2021

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BackgroundClear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer type with a high mortality rate. Due to a diverse range of biochemical alterations and a high level of tumor heterogeneity, it is crucial to select highly validated prognostic biomarkers to be able to identify subtypes of ccRCC early and apply precision medicine approaches.MethodsTranscriptome data of ccRCC and clinical traits of patients were obtained from the GSE126964 dataset of Gene Expression Omnibus and The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) database. Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening were applied to detect common differentially co-expressed genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, survival analysis, prognostic model establishment, and gene set enrichment analysis were also performed. Immunohistochemical analysis results of the expression levels of prognostic genes were obtained from The Human Protein Atlas. Single-gene RNA sequencing data were obtained from the GSE131685 and GSE171306 datasets.ResultsIn the present study, a total of 2,492 DEGs identified between ccRCC and healthy controls were filtered, revealing 1,300 upregulated genes and 1,192 downregulated genes. Using WGCNA, the turquoise module was identified to be closely associated with ccRCC. Hub genes were identified using the maximal clique centrality algorithm. After having intersected the hub genes and the DEGs in GSE126964 and TCGA-KIRC dataset, and after performing univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, ALDOB, EFHD1, and ESRRG were identified as significant prognostic factors in patients diagnosed with ccRCC. Single-gene RNA sequencing analysis revealed the expression profile of ALDOB, EFHD1, and ESRRG in different cell types of ccRCC.ConclusionsThe present results demonstrated that ALDOB, EFHD1, and ESRRG may act as potential targets for medical therapy and could serve as diagnostic biomarkers for ccRCC.

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Section: Metabolic Shift In Clear Cell Renal Cell Carcinomamentioning

confidence: 99%

Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

et al. 2021

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“…Neuroblastoma (NB) is an embryonic tumor derived from sympathetic neural crest cells ( 1 , 2 ). It is the most common type of extracranial solid tumor found in children and the most common type of malignant tumor found in infants and young children, with an incidence rate of 10.5 per million children younger than 14 years old ( 3 – 5 ). The site of the disease is concealed, and NB easily metastasizes ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Xie

Zhang

et al. 2020

Oncol Lett

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Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up-and 571 genes were downregulated, with 32 lncRNAs up-and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

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“…Recently, in neuroblastoma it has been reported that the oncogenic role of PTHrP is a consequence of its intracrine function, as downregulation of its receptor, PTH1R, increased anchorage independent growth and induced a more undifferentiated, invasive phenotype [ 14 ]. Interestingly, in oral cancer, in contrast to what we observed in laryngeal cancer, Chang et al recently reported that PTHrP promotes cell growth via an autocrine/paracrine pathway [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…The amino-terminal region of PTHrP (1–34) presents similarities to that of parathyroid hormone, including the PTH/PTHrP type 1 receptor (PTH1R), which is expressed at the plasma membrane of cell lines and tissues [ 11 ]. In vitro and in vivo evidences indicate that PTHrP is involved in tumor initiation, growth and metastatic spread [ 12 – 14 ]. Finally, the overexpression of PTHrP is associated with poorly differentiated oral squamous cell carcinoma, characterized by poor overall survival [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several authors indicated that PTHrP gene expression is regulated by HER1 signaling in a variety of normal and cancer cell types [ 14 , 23 – 27 ], thus contributing to the malignant behavior of tumor cells downstream of HER1 signaling. For example, in oral squamous cell carcinoma, PTHrP gene expression is up-regulated by HER1 signaling through the MAPK cascades and leads to enhanced cell proliferation, migration and invasion [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival

et al. 2022

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Background Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. Methods We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. Results The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62–22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19–105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04–0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04–0.91; p = 0.029). Conclusions In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

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Parathyroid hormone‐like hormone plays a dual role in neuroblastoma depending on PTH1R expression

Cited by 8 publications

References 48 publications

Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival

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