Abstract
Up to now, the serine-arginine protein kinase 1 (SRPK1) has been suggested as an important signal mediator, which is implicated in the development of cancers. Unfortunately, some molecular pathways in SRPK1-mediated epithelial-mesenchymal transition (EMT) in human spinal glioblastoma have been not elucidated. In this work, we detected the expression of SRPK1 in human spinal glioblastoma tissues and GBM cell lines and analyzed the relevant molecular proteins using in vitro experiments, including RT-PCR, gene silencing, and Western blot. In this study, RT-PCR and Western blot revealed that the expression of SRPK1 mRNA and protein became higher in all six spinal glioblastoma specimens; however, its expression was low in matched normal specimens. We also demonstrated SRPK1 expression facilitated the proliferation of U87 and U251 cells and inhibited the apoptosis in U87 and U251 cells. Also, SRPK1 promoted the expression of EMT-regulating markers, involving N-cadherin, Snail, and MMP9 and decreased the expression of mesenchymal marker E-cadherin. Moreover, knockdown of SRPK1 significantly inhibited the expression levels of p-Akt rather than t-Akt. In conclusion, knockdown of SRPK1 inhibited glioblastoma cell proliferation, invasion, and EMT process via suppressing p-Akt signaling pathway. This study also lays a new foundation for the clinically biological treatment.
Similar content being viewed by others
References
Baleriaux DL (1999) Spinal cord tumors. Eur Radiol 9:1252–1258
Cuadrado-Pereira M, Rodriguez-Saenz J, Andujar-Felix J (2007) Spinal cord high grade astrocytoma. Bol Asoc Med P R 99:60–63
Henson JW (2001) Spinal cord gliomas. Curr Opin Neurol 14:679–682
Houten JK, Weiner HL (2000) Pediatric intramedullary spinal cord tumors: special considerations. J Neurooncol 47:225–230
Townsend N, Handler M, Fleitz J, Foreman N (2004) Intramedullary spinal cord astrocytomas in children. Pediatr Blood Cancer 43:629–632
Wang F, Zhou J, Xie X, Hu J, Chen L, Hu Q et al (2015) Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1 in human ovarian cancer cells. Neoplasma 62(3):432–438
Keshwani MM, Aubol BE, Fattet L, Ma CT, Qiu J, Jennings PA et al (2015) Conserved proline-directed phosphorylation regulates SR protein conformation and splicing function. Biochem J 466(2):311–322
Lin JC, Lin CY, Tarn WY, Li FY (2014) Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. RNA 20(10):1621–1631
Gammons MV, Lucas R, Dean R, Coupland SE, Oltean S, Bates DO (2014) Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma. Br J Cancer 111(3):477–485
Aubol BE, Adams JA (2014) Recruiting a silent partner for activation of the protein kinase SRPK1. Biochemistry 53(28):4625–4634
Yan J, Zhang Y, Ren C, Shi W, Chen L. Involvement of nuclear protein C23 in activation of EGFR signaling in cervical cancer. Tumour Biol. 2015. [Epub ahead of print]
Pan Y, Zhang Y, Chen L, Liu Y, Feng Y, Yan J. The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression. Mol Neurobiol. 2015. [Epub ahead of print] PMID: 26245486
Ghosh G, Adams JA (2011) Phosphorylation mechanism and structure of serine-arginine protein kinases. FEBS J 278(4):587–597
Ren G, Sheng L, Liu H, Sun Y, An Y, Li Y (2015) The crucial role of SRPK1 in TGF-β-induced proliferation and apoptosis in the esophageal squamous cell carcinomas. Med Oncol 32(7):209
Hayes GM, Carrigan PE, Miller LJ (2007) Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas. Cancer Res 67:2072–2080
Zhou B, Li Y, Deng Q, Wang H, Wang Y, Cai B et al (2013) SRPK1 contributes to malignancy of hepatocellular carcinoma through a possible mechanism involving PI3K/Akt. Mol Cell Biochem 379:191–199
Niu H, Zhang X, Wang B, Zhou Z, Wang J, Xu Z. The clinical utility of image-guided iodine-125 seed in patients with unresectable pancreatic cancer. Tumour Biol. 2015. [Epub ahead of print] PMID: 26353858
Li K, Xu B, Xu G, Liu R (2015) CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma. Tumour Biol
Lv B, Yang X, Lv S, Wang L, Fan K, Shi R et al (2015) CXCR4 signaling induced epithelial-mesenchymal transition by PI3K/AKT and ERK pathways in glioblastoma. Mol Neurobiol 52(3):1263–1268
Lv S, Dai C, Liu Y, Sun B, Shi R, Han M et al (2015) Cell surface protein C23 affects EGF-EGFR induced activation of ERK and PI3K-AKT pathways. J Mol Neurosci 55(2):519–524
Wu J, Zhang X, Yan Y, Tang Z, Sun X, Huo G, et al. The Crucial Role of Cyclin-Dependent Kinase-5-Ataxia-Telangiectasia Mutated Axis in ICH-Induced Neuronal Injury of Rat Model. Mol Neurobiol. 2015 Nov 14. [Epub ahead of print] PMID: 26567107
Acknowledgments
This study is supported by the Chong Qing Natural Science Foundation (cstc2015jcyjA0526).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
For the use of clinical materials for research purposes, samples were obtained with prior written informed consents from the patients and approval from the Institutional Research Ethics Committees of the First Affiliated Hospital of Chongqing Medical University.
Conflict of Interest
The authors declare that they have no conflict of interest.
Additional information
This article has been retracted at the request of the Editor-in-Chief and the Publisher per the Committee on Publication Ethics guidelines. There is strong reason to believe that the peer review process was compromised. As such the validity of the content of this article cannot be verified.
An erratum to this article is available at http://dx.doi.org/10.1007/s12035-017-0662-8.
About this article
Cite this article
Liao, Z., Wu, J., Wu, M. et al. RETRACTED ARTICLE: The Critical Role of SRPK1 in EMT of Human Glioblastoma in the Spinal Cord. Mol Neurobiol 54, 1818–1824 (2017). https://doi.org/10.1007/s12035-016-9784-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-016-9784-7