Skip to main content

Advertisement

SpringerLink
Log in

Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

To explore the role of ribosomal protein S15A (RPS15A) in breast cancer. The Oncomine database was used to compare the expression of RPS15A in human breast cancer tissues and normal tissues. RPS15A in breast cancer cell line ZR-75-30 and BT474 was specifically knocked down using lentivirus-mediated short hairpin RNAs (shRNAs). RPS15A knockdown efficiency was validated by quantitative polymerase chain reaction and western blot analysis. Subsequently, the functional effects of RPS15A on proliferation of breast cancer cells were investigated by MTT, colony formation and flow cytometry assays. Functional analysis indicated that RPS15A knockdown could inhibit cell proliferation, induced cell cycle arrest and apoptosis. Mechanism analysis revealed RPS15A mediated apoptosis via activating of caspase-3 and PARP cleavage, upregulating of Bad and BAX and downregulating of Bcl-2. Our preliminary study highlighted the importance of RPS15A in breast cancer growth. The inhibition of RPS15A may be a promising therapeutic target for breast cancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Akiyama N, Matsuo Y, Sai H, Noda M, Kizakakondoh S (2000) Identification of a series of transforming growth factor Β-responsive genes by retrovirus-mediated gene trap screening. Mol Cell Biol 20:3266–3273

    Article  CAS  Google Scholar 

  • Amsterdam A, Sadler KC, Lai K, Farrington S, Bronson RT, Lees JA, Hopkins N (2004) Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biol 2:0690–0698

    Article  CAS  Google Scholar 

  • Besbes S, Mirshahi M, Pocard M, Billard C (2015) New dimension in therapeutic targeting of BCL-2 family proteins. Oncotarget 6:12862–12871

    Article  Google Scholar 

  • Bonham-Smith PC, Moloney MM (1994) Nucleotide and protein sequences of a cytoplasmic ribosomal protein S15a gene from Arabidopsis thaliana. Plant Physiol 106:401–402

    Article  CAS  Google Scholar 

  • Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR (2010) The BCL-2 family reunion. Mol Cell 37:299–310. https://doi.org/10.1016/j.molcel.2010.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hannemann J, Velds A, Halfwerk JB, Kreike B, Peterse JL, Vijver MJVD (2006) Classification of ductal carcinoma in situ by gene expression profiling. Breast Cancer Res 8:R61

    Article  Google Scholar 

  • Heeres JT, Hergenrother PJ (2007) Poly(ADP-ribose) makes a date with death. Curr Opin Chem Biol 11:644–653. https://doi.org/10.1016/j.cbpa.2007.08.038

    Article  CAS  PubMed  Google Scholar 

  • Jimenez L, Becerra A, Landa A (2004) Cloning, expression and partial characterization of a gene encoding the S15a ribosomal protein of Taenia solium. Parasitol Res 92:414–420. https://doi.org/10.1007/s00436-003-1021-4

    Article  PubMed  Google Scholar 

  • Karagianni M, Kaitelidou D, Kalokairinou A, Mantas J (2014) Breast cancer in social media: a literature review. Stud Health Technol Inform 202:321

    PubMed  Google Scholar 

  • Kavak E, Unlu M, Nister M, Koman A (2010) Meta-analysis of cancer gene expression signatures reveals new cancer genes, sage tags and tumor associated regions of co-regulation. Nucl Acids Res 38:7008–7021

    Article  CAS  Google Scholar 

  • Kelly GL, Strasser A (2011) The essential role of evasion from cell death in cancer. Adv Cancer Res 111:39–96. https://doi.org/10.1016/B978-0-12-385524-4.00002-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lavoie C, Tam R, Clark M, Lee H, Sonenberg N, Lasko P (1994) Suppression of a temperature-sensitive cdc33 mutation of yeast by a multicopy plasmid expressing a Drosophila ribosomal protein. J Biol Chem 269:14625–14630

    CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Maiyu X et al (2014) Down-regulation of ribosomal protein S15A mRNA with a short hairpin RNA inhibits human hepatic cancer cell growth in vitro. Gene 536:84–89

    Article  Google Scholar 

  • Mazumder S, Plesca D, Almasan A (2008) Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. Methods Mol Biol 414:13–21

    CAS  PubMed  Google Scholar 

  • Ottolini D, Calì T, Negro A, Brini M (2013) The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum Mol Genet 22:2152–2168

    Article  CAS  Google Scholar 

  • Rhodes D et al (2007) Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia 9:166–180

    Article  CAS  Google Scholar 

  • Ruggero D, Pandolfi PP (2003) Does the ribosome translate cancer? Nat Rev Cancer 3:179–192

    Article  CAS  Google Scholar 

  • Shen XC, Valencia CA, Szostak JW, Dong B, Liu R (2005) Scanning the human proteome for calmodulin-binding proteins. Proc Natl Acad Sci USA 102:5969–5974

    Article  CAS  Google Scholar 

  • Strasser A, Cory S, Adams JM (2011) Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J 30:3667–3683. https://doi.org/10.1038/emboj.2011.307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucl Acids Res 45:W98–W102

    Article  CAS  Google Scholar 

  • Yu X (2014) Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells. Biosci Rep 34:e00161–e00161

    PubMed  PubMed Central  Google Scholar 

  • Zeller KI, Jegga AG, Aronow BJ, O’Donnell KA, Chi VD (2003) An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol 4:54–56

    Article  Google Scholar 

  • Zhang C et al (2014a) HSPC111 governs breast cancer growth by regulating ribosomal biogenesis. Mol Cancer Res 12:583–594

    Article  CAS  Google Scholar 

  • Zhang C, Zhang T, Song E, Swa H, Chen X, Zheng L (2014b) Ribosomal protein S15A augments human osteosarcoma cell proliferation in vitro. Cancer Biother Radiopharm 29:451–456

    Article  CAS  Google Scholar 

  • Zhang GQ, He C, Tao L, Liu F (2015) Role of DJ-1 siRNA in reverse sensitivity of breast cancer cells to chemotherapy and its possible mechanism. Int J Clin Exp Pathol 8:6944–6951

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao X et al (2015) Decreased expression of RPS15A suppresses proliferation of lung cancer cells. Tumor Biol 36:6733–6740

    Article  CAS  Google Scholar 

  • Zhou W, Shi G, Zhang Q, Wu Q, Li B, Zhang Z (2014) MicroRNA-20b promotes cell growth of breast cancer cells partly via targeting phosphatase and tensin homologue (PTEN). Cell Biosci 4:62. https://doi.org/10.1186/2045-3701-4-62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Project from Natural Science Foundation of Zhejiang Province (LY18H160033).

Author information

Author notes

  1. Weiliang Feng and Chenlu Liang contributed equally.

Authors and Affiliations

  1. Department of Breast Surgery, Zhejiang Cancer Hospital, No. 1 East Banshan Road, Hangzhou, 310022, China

    Weiliang Feng, Chenlu Liang, Chen Wang, Xingfei Yu & Hongjian Yang

  2. Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, China

    Chenlu Liang

  3. Department of Pharmacy, Zhejiang Cancer Hospital, No. 1 East Banshan Road, Hangzhou, 310022, China

    Qinglin Li

Authors
  1. Weiliang Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chenlu Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xingfei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qinglin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongjian Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hongjian Yang.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 552 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, W., Liang, C., Wang, C. et al. Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro. Cytotechnology 70, 1315–1323 (2018). https://doi.org/10.1007/s10616-018-0221-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-018-0221-9

Keywords

Search

Navigation