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Published in: World Journal of Surgical Oncology 1/2016

Open Access 01-12-2016 | Research

Knockdown of ribosomal protein S15A induces human glioblastoma cell apoptosis

Authors: Chen Zhang, Jiqiang Fu, Fei Xue, Bomi Ryu, Ting Zhang, Shuili Zhang, Jingyu Sun, Xinxin Xu, Zhaoli Shen, Longpo Zheng, Xianzhen Chen

Published in: World Journal of Surgical Oncology | Issue 1/2016

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Abstract

Background

RPS15A is a ribosome protein that is highly conserved in many organisms from yeast to human. A number of studies implied its role in promoting cancer cell growth.

Methods

Here, we firstly conducted RPS15A gene expression analysis in brain cancer using Oncomine database and found RPS15A was remarkably overexpressed in glioblastoma (GBM) compared with that in normal tissues. Then, the expression of RPS15A was specifically silenced in GBM cell line U251 using lentiviral-mediated RNA interference technique. We further investigated the effect of RPS15A knockdown in U251 cells using MTT assay, colony formation test, and flow cytometry analysis. We detected the protein level of Bcl-2 and poly (ADP-ribose) polymerase (PARP) as well as activation of caspase-3.

Results

Our results showed that the knockdown of RPS15A could inhibit cancer cell growth and colony formation in vitro, as well as induced cell cycle arrest at G0/G1 phase and cell apoptosis. In addition, Western blot analysis indicated that the knockdown of RPS15A could significantly inhibit bcl-2 and activate caspase-3 and PARP.

Conclusions

Our findings suggest RPS15A may play an important role in the progression of GBM and lentiviral-mediated silencing of RPS15A could be an effective tool in GBM treatment.
Literature
1.
go back to reference Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain tumours. Brain Pathol. 1993;3(3):255–68.CrossRefPubMed Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain tumours. Brain Pathol. 1993;3(3):255–68.CrossRefPubMed
2.
go back to reference Kleihues P, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 2002;61(3):215–25. discussion 226-9. Kleihues P, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 2002;61(3):215–25. discussion 226-9.
3.
go back to reference Kang TW, et al. Growth arrest and forced differentiation of human primary glioblastoma multiforme by a novel small molecule. Sci Rep. 2014;4:5546. Kang TW, et al. Growth arrest and forced differentiation of human primary glioblastoma multiforme by a novel small molecule. Sci Rep. 2014;4:5546.
4.
go back to reference Jensen SA, et al. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Transl Med. 2013;5(209):2124–34. Jensen SA, et al. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Transl Med. 2013;5(209):2124–34.
5.
go back to reference Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.
7.
8.
go back to reference Ciarmatori S, et al. Overlapping functions of the pRb family in the regulation of rRNA synthesis. Mol Cell Biol. 2001;21(17):5806–14. Ciarmatori S, et al. Overlapping functions of the pRb family in the regulation of rRNA synthesis. Mol Cell Biol. 2001;21(17):5806–14.
9.
go back to reference Barna M, et al. Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature. 2008;456(7224):971–5. Barna M, et al. Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature. 2008;456(7224):971–5.
10.
go back to reference Wool IG, Chan YL, Gluck A. Structure and evolution of mammalian ribosomal proteins. Biochem Cell Biol. 1995;73(11-12):933–47.CrossRefPubMed Wool IG, Chan YL, Gluck A. Structure and evolution of mammalian ribosomal proteins. Biochem Cell Biol. 1995;73(11-12):933–47.CrossRefPubMed
11.
go back to reference Chan YL, et al. The primary structure of rat ribosomal protein S15a. Biochem Biophys Res Commun. 1994;200(3):1498–504. Chan YL, et al. The primary structure of rat ribosomal protein S15a. Biochem Biophys Res Commun. 1994;200(3):1498–504.
12.
go back to reference Zhao X, et al. Decreased expression of RPS15A suppresses proliferation of lung cancer cells. Tumour Biol. 2015;36(9):6733-40. Zhao X, et al. Decreased expression of RPS15A suppresses proliferation of lung cancer cells. Tumour Biol. 2015;36(9):6733-40.
13.
go back to reference Zhang C, et al. Ribosomal protein S15A augments human osteosarcoma cell proliferation in vitro. Cancer Biother Radiopharm. 2014;29(10):451–6. Zhang C, et al. Ribosomal protein S15A augments human osteosarcoma cell proliferation in vitro. Cancer Biother Radiopharm. 2014;29(10):451–6.
14.
go back to reference Xu M, et al. Down-regulation of ribosomal protein S15A mRNA with a short hairpin RNA inhibits human hepatic cancer cell growth in vitro. Gene. 2014;536(1):84–9. Xu M, et al. Down-regulation of ribosomal protein S15A mRNA with a short hairpin RNA inhibits human hepatic cancer cell growth in vitro. Gene. 2014;536(1):84–9.
15.
go back to reference Rhodes DR, et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004;6(1):1–6. Rhodes DR, et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004;6(1):1–6.
16.
go back to reference Bredel M, et al. Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res. 2005;65(19):8679–89. Bredel M, et al. Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res. 2005;65(19):8679–89.
17.
go back to reference French PJ, et al. Gene expression profiles associated with treatment response in oligodendrogliomas. Cancer Res. 2005;65(24):11335–44. French PJ, et al. Gene expression profiles associated with treatment response in oligodendrogliomas. Cancer Res. 2005;65(24):11335–44.
18.
go back to reference Murat A, et al. Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol. 2008;26(18):3015–24. Murat A, et al. Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol. 2008;26(18):3015–24.
19.
go back to reference Shai R, et al. Gene expression profiling identifies molecular subtypes of gliomas. Oncogene. 2003;22(31):4918–23. Shai R, et al. Gene expression profiling identifies molecular subtypes of gliomas. Oncogene. 2003;22(31):4918–23.
20.
go back to reference Sun L, et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 2006;9(4):287–300. Sun L, et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 2006;9(4):287–300.
21.
go back to reference Vermes I, et al. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 1995;184(1):39–51. Vermes I, et al. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 1995;184(1):39–51.
22.
go back to reference Favaloro B, et al. Role of apoptosis in disease. Aging (Albany NY). 2012;4(5):330–49. Favaloro B, et al. Role of apoptosis in disease. Aging (Albany NY). 2012;4(5):330–49.
23.
go back to reference Kenmochi N, et al. A map of 75 human ribosomal protein genes. Genome Res. 1998;8(5):509–23. Kenmochi N, et al. A map of 75 human ribosomal protein genes. Genome Res. 1998;8(5):509–23.
24.
go back to reference Zhao X, et al. Decreased expression of RPS15A suppresses proliferation of lung cancer cells. Tumour Biol. 2015;36(9):6733–40.CrossRefPubMed Zhao X, et al. Decreased expression of RPS15A suppresses proliferation of lung cancer cells. Tumour Biol. 2015;36(9):6733–40.CrossRefPubMed
25.
go back to reference Li P, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997;91(4):479–89.CrossRefPubMed Li P, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997;91(4):479–89.CrossRefPubMed
26.
go back to reference Swanton E, et al. Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. Oncogene. 1999;18(10):1781–7.CrossRefPubMed Swanton E, et al. Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. Oncogene. 1999;18(10):1781–7.CrossRefPubMed
27.
go back to reference Perry DK, et al. Bcl-2 acts upstream of the PARP protease and prevents its activation. Cell Death Differ. 1997;4(1):29–33.CrossRefPubMed Perry DK, et al. Bcl-2 acts upstream of the PARP protease and prevents its activation. Cell Death Differ. 1997;4(1):29–33.CrossRefPubMed
28.
go back to reference Veenman L, Gavish M, Kugler W. Apoptosis induction by erucylphosphohomocholine via the 18 kDa mitochondrial translocator protein: implications for cancer treatment. Anticancer Agents Med Chem. 2014;14(4):559–77.CrossRefPubMed Veenman L, Gavish M, Kugler W. Apoptosis induction by erucylphosphohomocholine via the 18 kDa mitochondrial translocator protein: implications for cancer treatment. Anticancer Agents Med Chem. 2014;14(4):559–77.CrossRefPubMed
Metadata
Title
Knockdown of ribosomal protein S15A induces human glioblastoma cell apoptosis
Authors
Chen Zhang
Jiqiang Fu
Fei Xue
Bomi Ryu
Ting Zhang
Shuili Zhang
Jingyu Sun
Xinxin Xu
Zhaoli Shen
Longpo Zheng
Xianzhen Chen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2016
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-016-0891-8

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