Skip to main content

Advertisement

SpringerLink
Log in

hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR

  • Original Article
  • Published:
Tumor Biology

Abstract

Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.

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
Fig. 5

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  2. Crawford ED, Higano CS, Shore ND, Hussain M, Petrylak DP. Treating patients with metastatic castration-resistant prostate cancer: a comprehensive review of available therapies. J Urol 2015.

  3. Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 2010;24(18):1967–2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ. Biological functions of microRNAs: a review. J Physiol Biochem. 2011;67(1):129–39.

    Article  CAS  PubMed  Google Scholar 

  5. Fang YX, Gao WQ. Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene. 2014;33(2):135–47.

    Article  CAS  PubMed  Google Scholar 

  6. Boll K, Reiche K, Kasack K, Morbt N, Kretzschmar AK, Tomm JM, Verhaegh G, Schalken J, von Bergen M, Horn F, Hackermuller J. MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene. 2013;32(3):277–85.

    Article  CAS  PubMed  Google Scholar 

  7. Kojima S, Enokida H, Yoshino H, Itesako T, Chiyomaru T, Kinoshita T, Fuse M, Nishikawa R, Goto Y, Naya Y, Nakagawa M, Seki N. The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer. J Hum Genet. 2014;59(2):78–87.

    Article  CAS  PubMed  Google Scholar 

  8. Xu B, Wang N, Wang X, Tong N, Shao N, Tao J, Li P, Niu X, Feng N, Zhang L, Hua L, Wang Z, Chen M. MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. Prostate. 2012;72(11):1171–8.

    Article  CAS  PubMed  Google Scholar 

  9. Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, Gerald WL. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010;18(1):11–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kroiss A, Vincent S, Decaussin-Petrucci M, Meugnier E, Viallet J, Ruffion A, Chalmel F, Samarut J, Allioli N. Androgen-regulated microRNA-135a decreases prostate cancer cell migration and invasion through downregulating ROCK1 and ROCK2. Oncogene. 2015;34(22):2846–55.

    Article  CAS  PubMed  Google Scholar 

  11. Setlur SR, Royce TE, Sboner A, Mosquera JM, Demichelis F, Hofer MD, Mertz KD, Gerstein M, Rubin MA. Integrative microarray analysis of pathways dysregulated in metastatic prostate cancer. Cancer Res. 2007;67(21):10296–303.

    Article  CAS  PubMed  Google Scholar 

  12. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  Google Scholar 

  13. Nakabayashi M, Hayes J, Taplin ME, Lefebvre P, Lafeuille MH, Pomerantz M, Sweeney C, Duh MS, Kantoff PW. Clinical predictors of survival in men with castration-resistant prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal disease. Cancer. 2013;119(16):2990–8.

    Article  PubMed  Google Scholar 

  14. Hendriks LE, Smit EF, Vosse BA, Mellema WW, Heideman DA, Bootsma GP, Westenend M, Pitz C, de Vries GJ, Houben R, Grunberg K, Bendek M, Speel EJ, Dingemans AM. EGFR mutated non-small cell lung cancer patients: more prone to development of bone and brain metastases? Lung Cancer. 2014;84(1):86–91.

    Article  CAS  PubMed  Google Scholar 

  15. Nickerson NK, Mohammad KS, Gilmore JL, Crismore E, Bruzzaniti A, Guise TA, Foley J. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad. PLoS One. 2012;7(1):e30255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chang YS, Chen WY, Yin JJ, Sheppard-Tillman H, Huang J, Liu YN. EGF Receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1. Cancer Res 2015.

  17. Siu MK, Abou-Kheir W, Yin JJ, Chang YS, Barrett B, Suau F, Casey O, Chen WY, Fang L, Hynes P, Hsieh YY, Liu YN, Huang J, Kelly K. Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. Oncotarget. 2014;5(11):3770–84.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yang X, Yang K, Kuang K. The efficacy and safety of EGFR inhibitor monotherapy in non-small cell lung cancer: a systematic review. Curr Oncol Rep. 2014;16(6):390.

    Article  PubMed  Google Scholar 

  19. Ojemuyiwa MA, Madan RA, Dahut WL. Tyrosine kinase inhibitors in the treatment of prostate cancer: taking the next step in clinical development. Expert Opin Emerg Drugs. 2014;19(4):459–70.

    Article  CAS  PubMed  Google Scholar 

  20. Chen Q, Quan Q, Ding L, Hong X, Zhou N, Liang Y, Wu H. Continuation of epidermal growth factor receptor tyrosine kinase inhibitor treatment prolongs disease control in non-small-cell lung cancers with acquired resistance to EGFR tyrosine kinase inhibitors. Oncotarget 2015.

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China

    Bin Xu, Tao Tao, Yiduo Wang, Yeqing Huang, Shuqiu Chen, Weidong Zhu & Ming Chen

  2. Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China

    Bin Xu, Tao Tao, Yiduo Wang, Yeqing Huang & Ming Chen

  3. Department of Immunology, Bengbu Medical College, Bengbu, China

    Fang Fang

Authors
  1. Bin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yiduo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yeqing Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuqiu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Weidong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ming Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming Chen.

Ethics declarations

Funding

This study was supported by the National Natural Science Foundation of China (nos. 81202034 and 81370849), the Natural Science Foundation of Jiangsu Province (BK2012336 and BL2013032), Nanjing City (201201053), Southeast University (3290002402), and the Science Foundation of Ministry of Education of China (20120092120071).

Conflicts of interest

None

Additional information

Bin Xu, Tao Tao, Yiduo Wang, and Fang Fang contributed equally to this work.

Electronic supplementary material

Supplementary Figure 1

MiR-135a potentially targets multiple oncogenic pathways. A. miR-135a potentially targets multiple components of each indicated oncogenic pathway as predicted by microRNA.org. Shown are the gene names, number of potential binding sites, gene expression changes in cells overexpressing miR-135a (data retrieved form GSE45620), and the affected pathways. (GIF 41 kb)

High resolution image (TIFF 860 kb)

Fig7

B. Schematic representation of the binding site of miR-135a to target transcripts as predicted by microRNA.org. (GIF 80 kb)

High resolution image (TIFF 2709 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, B., Tao, T., Wang, Y. et al. hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR. Tumor Biol. 37, 14141–14151 (2016). https://doi.org/10.1007/s13277-016-5196-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5196-6

Keywords

Search

Navigation