Research Paper Volume 11, Issue 23 pp 11136—11147
Ninjurin2 overexpression promotes glioma cell growth
- 1 Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
- 2 Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- 3 Department of Chemoradiation Oncology, The First affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 4 Department of Neurosurgery, Nanjing Medical University Affiliated Changzhou No. 2 People’s Hospital, Changzhou, Jiangsu, China
Received: August 29, 2019 Accepted: November 18, 2019 Published: December 2, 2019
https://doi.org/10.18632/aging.102515How to Cite
Copyright © 2019 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Ninjurin2 (Ninj2) is an adhesion protein expressed in neurons and glial cells. The current study tested its expression and potential functions in human glioma. We show that Ninj2 mRNA and protein levels are significantly upregulated in human glioma cells and tissues. In established and primary human glioma cells, Ninj2 shRNA or knockout (by CRISPR/Cas9 gene editing) potently inhibited cell survival, growth, proliferation, cell migration and invasion, while inducing apoptosis activation. Contrarily, ectopic overexpression of Ninj2 promoted glioma cell progression in vitro. In human glioma tissues and cells, Ninj2 co-immunoprecipitated with multiple receptor tyrosine kinases (EGFR, PDGFRβ and FGFR), required for downstream Akt and Erk activation. Akt and Erk activation was potently inhibited by Ninj2 shRNA or knockout, but enhanced with ectopic Ninj2 overexpression in glioma cells. In summary, we show that Ninj2 overexpression promotes glioma cell growth.
Abbreviations
Co-IP: Co-immunoprecipitation; DMEM: Dulbecco’s modified Eagle’s medium; FBS: fetal bovine serum; Ninj1: Ninjurin1; Ninj2: Ninjurin2; qPCR: quantitative real-time reverse transcriptase polymerase chain reaction; PI: propidium iodide; SD: standard deviation; TdT: terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).