Dataset Information

PELP1 promotes glioblastoma progression by enhancing Wnt/?-catenin signaling.

ABSTRACT: Background:Glioblastoma (GBM) is a deadly neoplasm of the central nervous system. The molecular mechanisms and players that contribute to GBM development is incompletely understood. Methods:The expression of PELP1 in different grades of glioma and normal brain tissues was analyzed using immunohistochemistry on a tumor tissue array. PELP1 expression in established and primary GBM cell lines was analyzed by Western blotting. The effect of PELP1 knockdown was studied using cell proliferation, colony formation, migration, and invasion assays. Mechanistic studies were conducted using RNA-seq, RT-qPCR, immunoprecipitation, reporter gene assays, and signaling analysis. Mouse orthotopic models were used for preclinical evaluation of PELP1 knock down. Results:Nuclear receptor coregulator PELP1 is highly expressed in gliomas compared to normal brain tissues, with the highest expression in GBM. PELP1 expression was elevated in established and patient-derived GBM cell lines compared to normal astrocytes. Knockdown of PELP1 resulted in a significant decrease in cell viability, survival, migration, and invasion. Global RNA-sequencing studies demonstrated that PELP1 knockdown significantly reduced the expression of genes involved in the Wnt/?-catenin pathway. Mechanistic studies demonstrated that PELP1 interacts with and functions as a coactivator of ?-catenin. Knockdown of PELP1 resulted in a significant increase in survival of mice implanted with U87 and GBM PDX models. Conclusions:PELP1 expression is upregulated in GBM and PELP1 signaling via ?-catenin axis contributes to GBM progression. Thus, PELP1 could be a potential target for the development of therapeutic intervention in GBM.

SUBMITTER: Sareddy GR

PROVIDER: S-EPMC7147719 | biostudies-literature | 2019 May-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling.

Sareddy Gangadhara R GR Pratap Uday P UP Viswanadhapalli Suryavathi S Venkata Prabhakar Pitta PP Nair Binoj C BC Krishnan Samaya Rajeshwari SR Zheng Siyuan S Gilbert Andrea R AR Brenner Andrew J AJ Brann Darrell W DW Vadlamudi Ratna K RK

Neuro-oncology advances 20190501 1

<h4>Background</h4>Glioblastoma (GBM) is a deadly neoplasm of the central nervous system. The molecular mechanisms and players that contribute to GBM development is incompletely understood.<h4>Methods</h4>The expression of PELP1 in different grades of glioma and normal brain tissues was analyzed using immunohistochemistry on a tumor tissue array. PELP1 expression in established and primary GBM cell lines was analyzed by Western blotting. The effect of PELP1 knockdown was studied using cell proli ...[more]

PMID: 32309805

Similar Datasets

Project description:BackgroundThe expression of forkhead box protein H1 (FOXH1) is frequently upregulated in various cancers. However, the molecular mechanisms underlying the association between FOXH1 expression and lung cancer progression still remain poorly understood. Thus, the main objective of this study is to explore the role of FOXH1 in lung cancer.MethodsThe Cancer Genome Atlas dataset was used to investigate FOXH1 expression in lung cancer tissues, and the Kaplan-Meier plotter dataset was used to determine the role of FOXH1 in patient prognosis. A549 and PC9 cells were transfected with short hairpin RNA targeting FOXH1 mRNA. The Cell Counting Kit-8, colony formation, soft agar, wound healing, transwell invasion and flow cytometry assays were performed to evaluate proliferation, migration and invasion of lung cancer cells. Tumorigenicity was examined in a BALB/c nude mice model. Western blot analysis was performed to assess the molecular mechanisms, and β-catenin activity was measured by a luciferase reporter system assay.ResultsHigher expression level of FOXH1 was observed in tumor tissue than in normal tissue, and this was associated with poor overall survival. Knockdown of FOXH1 significantly inhibited lung cancer cell proliferation, migration, invasion, and cycle. In addition, the mouse xenograft model showed that knockdown of FOXH1 suppressed tumor growth in vivo. Further experiments revealed that FOXH1 depletion inhibited the epithelial-mesenchymal transition of lung cancer cells by downregulating the expression of mesenchymal markers (Snail, Slug, matrix metalloproteinase-2, N-cadherin, and Vimentin) and upregulating the expression of an epithelial marker (E-cadherin). Moreover, knockdown of FOXH1 significantly downregulated the activity of β-catenin and its downstream targets, p-GSK-3β and cyclin D1.ConclusionFOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/β-catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer.

Dataset Information

PELP1 promotes glioblastoma progression by enhancing Wnt/?-catenin signaling.

Publications

PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets