PBX3/MEK/ERK1/2/LIN28/let-7b positive feedback loop enhances mesenchymal phenotype to promote glioblastoma migration and invasion

Journal of Experimental & Clinical Cancer Research : CR
Xiupeng XuJing Ji

Abstract

Brain invasion by glioblastoma (GBM) determines recurrence and prognosis in patients, which is, in part, attributed to increased mesenchymal transition. Here, we report evidence favoring such a role for the Pre-B-cell leukemia homebox (PBX) family member PBX3. Western blot, immunohistochemistry, qRT-PCR and datasets mining were used to determined proteins or genes expression levels. Wound-healing and transwell assays were used to examine the invasive abilities of GBM cells. Dual-luciferase reporter assays were used to determine how let-7b regulates PBX3. Chromatin-immunoprecipitation (ChIP) and rescue experiments were performed to investigate the involved molecular mechanisms. Orthotopic mouse models were used to assess the role of PBX3 in vivo. We found that PBX3 expression levels positively correlated with glioma mesenchymal markers. Ectopic expression of PBX3 promoted invasive phenotypes and triggered the expression of mesenchymal markers, whereas depletion of PBX3 reduced GBM cell invasive abilities and decreased the expression of mesenchymal markers. In addition, inhibition of PBX3 attenuated transforming growth factor-β (TGFβ)-induced GBM mesenchymal transition. Mechanistic studies revealed that PBX3 mediated GBM mesenchy...Continue Reading

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Citations

Jun 23, 2020·Experimental and Therapeutic Medicine·Xiang AoYing Liu
Jan 9, 2020·Journal of Neuro-oncology·Tristan de MooijIan F Parney
Feb 20, 2020·Cancers·Richard Morgan, Hardev S Pandha
Mar 26, 2021·Acta Neuropathologica Communications·Yona KimSun Ha Paek
May 25, 2021·Journal of the Chinese Medical Association : JCMA·Xian LiuLiang-Ting Lin
May 17, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yi YangXiaoming Lin
Sep 28, 2021·The Cancer Journal·Andrew J ScottDaniel R Wahl

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Datasets Mentioned

BETA
GSE4290
GSE59612

Methods Mentioned

BETA
surgical resection
total
transfection
PCR
immunoprecipitation
Assay
enzyme-linked immunosorbent assay
PMA
ChIP
ELISA

Software Mentioned

GraphPad
Gene Cluster
GSEA
GraphPad Prism

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