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PELP1 signaling contributes to medulloblastoma progression by regulating the NF‐κB pathway
Author(s) -
Luo Yiliao,
Li Mengxing,
Pratap Uday P.,
Viswanadhapalli Suryavathi,
Liu Junhao,
Venkata Prabhakar P.,
Altwegg Kristin A.,
Palacios Bridgitte E.,
Li Xiaonan,
Chen Yihong,
Rao Manjeet K.,
Brenner Andrew J.,
Sareddy Gangadhara R.,
Vadlamudi Ratna K.
Publication year - 2020
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23152
Subject(s) - gene knockdown , biology , cancer research , microarray analysis techniques , signal transduction , extracellular matrix , nf κb , medulloblastoma , gene , microbiology and biotechnology , gene expression , genetics
Abstract Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline‐, glutamic acid‐, and leucine‐rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA‐sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1‐regulated genes were negatively correlated with nuclear factor‐κB (NF‐κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF‐κB target genes, NF‐κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.