Skip to main content
Log in

Expression patterns and bioinformatic analysis of miR-1260a and miR-1274a in Prostate Cancer Tunisian patients

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Currently, microRNAs (miRs) represent great biomarkers in cancer due to their stability and their potential role in diagnosis, prognosis and therapy. This study aims to evaluate the expression levels of miRs-1260 and -1274a in prostate cancer (PC) samples and to identify their eventual targets by using bioinformatic analysis. In this project, we evaluated the expression status of miRs-1260 and -1274a in 86 PC patients and 19 controls by using real-time quantitative PCR and 2−ΔΔCt method. Moreover, we retrieved validated and predicted targets of miRs from several datasets by using the “multiMir” R/Bioconductor package. We have found that miRs-1260 and -1274a were over-expressed in PC patients compared to controls (p < 1 × 10−5). Moreover ROC curve for miRs-1260 and 1274a showed a good performance to distinguish between controls group and PC samples with an area under the ROC curve of 0.897 and 0.784 respectively. However, no significant association could be shown between these two miRs and clinical parameters such as PSA levels, Gleason score, tumor stage, D’Amico classification, lymph node metastasis statues, tumor recurrence, metastasis status and progression after a minimum of 5 years follow-up. Finally, a bioinformatic analysis revealed the association between these two miRs and several targets implicated in prostate cancer initiation pathways.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA 67(1):7–30. https://doi.org/10.3322/caac.21387

    Article  PubMed  Google Scholar 

  2. Souiden Y, Mahdouani M, Chaieb K, Bakhrouf A, Mahdouani K (2012) Lack of association of CYP1A1 polymorphism with prostate cancer susceptibility of Tunisian men. Genet Test Mol Biomark 16(7):661–666. https://doi.org/10.1089/gtmb.2011.0212

    Article  CAS  Google Scholar 

  3. Keto CJ, Freedland SJA, Risk-Stratified Approach to prostate-specific antigen screening. Eur Urol 59(4):506–508. https://doi.org/10.1016/j.eururo.2011.01.029

    Article  Google Scholar 

  4. Nadler RB, Humphrey PA, Smith DS, Catalona WJ, Ratliff TL (1995) Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J Urol 154(2 Pt 1):407–413

    Article  CAS  Google Scholar 

  5. Kirby M, Hirst C, Crawford ED (2011) Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 65(11):1180–1192. https://doi.org/10.1111/j.1742-1241.2011.02799.x

    Article  CAS  PubMed  Google Scholar 

  6. Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, Huang WC, Sun TH, Tu SJ, Lee WH, Chiew MY, Tai CS, Wei TY, Tsai TR, Huang HT, Wang CY, Wu HY, Ho SY, Chen PR, Chuang CH, Hsieh PJ, Wu YS, Chen WL, Li MJ, Wu YC, Huang XY, Ng FL, Buddhakosai W, Huang PC, Lan KC, Huang CY, Weng SL, Cheng YN, Liang C, Hsu WL, Huang HD (2018) miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res 46(D1):D296–D302. https://doi.org/10.1093/nar/gkx1067

    Article  PubMed  Google Scholar 

  7. Bartels CL, Tsongalis GJ (2010) MicroRNAs: novel biomarkers for human cancer. Ann Biol Clin 68(3):263–272. https://doi.org/10.1684/abc.2010.0429

    Article  CAS  Google Scholar 

  8. Iorio MV, Croce CM (2012) microRNA involvement in human cancer. Carcinogenesis 33(6):1126–1133. https://doi.org/10.1093/carcin/bgs140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Luu HN, Lin H-Y, Sørensen KD, Ogunwobi OO, Kumar N, Chornokur G, Phelan C, Jones D, Kidd L, Batra J, Yamoah K, Berglund A, Rounbehler RJ, Yang M, Lee SH, Kang N, Kim SJ, Park JY, Di Pietro G (2017) miRNAs associated with prostate cancer risk and progression. BMC Urol 17(1):18. https://doi.org/10.1186/s12894-017-0206-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Madhavan D, Peng C, Wallwiener M, Zucknick M, Nees J, Schott S, Rudolph A, Riethdorf S, Trumpp A, Pantel K, Sohn C, Chang-Claude J, Schneeweiss A, Burwinkel B (2016) Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis. Carcinogenesis 37(5):461–470. https://doi.org/10.1093/carcin/bgw008

    Article  CAS  PubMed  Google Scholar 

  11. Sand M, Skrygan M, Sand D, Georgas D, Gambichler T, Hahn SA, Altmeyer P, Bechara FG (2013) Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi. Cell Tissue Res 351(1):85–98. https://doi.org/10.1007/s00441-012-1514-5

    Article  CAS  PubMed  Google Scholar 

  12. Yan H, Wang S, Yu H, Zhu J, Chen C (2013) Molecular pathways and functional analysis of miRNA expression associated with paclitaxel-induced apoptosis in hepatocellular carcinoma cells. Pharmacology 92(3–4):167–174. https://doi.org/10.1159/000354585

    Article  CAS  PubMed  Google Scholar 

  13. Zheng G, Du L, Yang X, Zhang X, Wang L, Yang Y, Li J, Wang C (2014) Serum microRNA panel as biomarkers for early diagnosis of colorectal adenocarcinoma. Br J Cancer 111(10):1985–1992. https://doi.org/10.1038/bjc.2014.489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dai F, Mei L, Meng S, Ma Z, Guo W, Zhou J, Zhang J (2017) The global expression profiling in esophageal squamous cell carcinoma. Genomics 109(3–4):241–250. https://doi.org/10.1016/j.ygeno.2017.04.005

    Article  CAS  PubMed  Google Scholar 

  15. Yoshino H, Yonezawa T, Yonemori M, Miyamoto K, Sakaguchi T, Sugita S, Osako Y, Tatarano S, Nakagawa M, Enokida H (2018) Downregulation of microRNA-1274a induces cell apoptosis through regulation of BMPR1B in clear cell renal cell carcinoma. Oncol Rep 39(1):173–181. https://doi.org/10.3892/or.2017.6098

    Article  CAS  PubMed  Google Scholar 

  16. Halvorsen AR, Kristensen G, Embleton A, Adusei C, Barretina-Ginesta MP, Beale P, Helland A (2017) Evaluation of prognostic and predictive significance of circulating microRNAs in ovarian cancer patients. Dis Mark 2017:3098542. https://doi.org/10.1155/2017/3098542

    Article  CAS  Google Scholar 

  17. Wang GJ, Liu GH, Ye YW, Fu Y, Zhang XF (2015) The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating cancer cell proliferation and migration via directly targeting FOXO4. Biochem Biophys Res Commun 459(4):629–635. https://doi.org/10.1016/j.bbrc.2015.02.160

    Article  CAS  PubMed  Google Scholar 

  18. Kristensen H, Thomsen AR, Haldrup C, Dyrskjot L, Hoyer S, Borre M, Mouritzen P, Orntoft TF, Sorensen KD (2016) Novel diagnostic and prognostic classifiers for prostate cancer identified by genome-wide microRNA profiling. Oncotarget 7(21):30760–30771. https://doi.org/10.18632/oncotarget.8953

    Article  PubMed  PubMed Central  Google Scholar 

  19. Moltzahn F, Olshen AB, Baehner L, Peek A, Fong L, Stoppler H, Simko J, Hilton JF, Carroll P, Blelloch R (2011) Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res 71(2):550–560. https://doi.org/10.1158/0008-5472.can-10-1229

    Article  CAS  PubMed  Google Scholar 

  20. Hessvik NP, Phuyal S, Brech A, Sandvig K, Llorente A (2012) Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim Biophys Acta 1819(11–12):1154–1163. https://doi.org/10.1016/j.bbagrm.2012.08.016

    Article  CAS  PubMed  Google Scholar 

  21. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  Google Scholar 

  22. Ru Y, Kechris KJ, Tabakoff B, Hoffman P, Radcliffe RA, Bowler R, Mahaffey S, Rossi S, Calin GA, Bemis L, Theodorescu D (2014) The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Nucleic Acids Res 42(17):e133. https://doi.org/10.1093/nar/gku631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sales G, Calura E, Cavalieri D, Romualdi C (2012) graphite: a bioconductor package to convert pathway topology to gene network. BMC Bioinform 13:20. https://doi.org/10.1186/1471-2105-13-20

    Article  Google Scholar 

  24. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798

    Article  CAS  Google Scholar 

  25. Betel D, Koppal A, Agius P, Sander C, Leslie C (2010) Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 11(8):R90. https://doi.org/10.1186/gb-2010-11-8-r90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866. https://doi.org/10.1038/nrc1997

    Article  CAS  Google Scholar 

  27. Xie J, Chen M, Zhou J, Mo MS, Zhu LH, Liu YP, Gui QJ, Zhang L, Li GQ (2014) miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing epidermal growth factor receptor expression. Oncol Rep 31(4):1715–1722. https://doi.org/10.3892/or.2014.3052

    Article  CAS  PubMed  Google Scholar 

  28. Fujita Y, Yagishita S, Hagiwara K, Yoshioka Y, Kosaka N, Takeshita F, Fujiwara T, Tsuta K, Nokihara H, Tamura T, Asamura H, Kawaishi M, Kuwano K, Ochiya T (2015) The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther 23(4):717–727. https://doi.org/10.1038/mt.2015.10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yi Z, Fu Y, Zhao S, Zhang X, Ma C (2010) Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. J Cancer Res Clin Oncol 136(6):855–862. https://doi.org/10.1007/s00432-009-0726-x

    Article  CAS  PubMed  Google Scholar 

  30. Latchana N, Regan K, Howard JH, Aldrink JH, Ranalli MA, Peters SB, Zhang X, Gru A, Payne PRO, Suarez-Kelly LP, Carson WE 3rd (2016) Global microRNA profiling for diagnostic appraisal of melanocytic Spitz tumors. J Surg Res 205(2):350–358. https://doi.org/10.1016/j.jss.2016.06.085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Khan FH, Pandian V, Ramraj S, Aravindan S, Herman TS, Aravindan N (2015) Reorganization of metastamiRs in the evolution of metastatic aggressive neuroblastoma cells. BMC Genomics 16:501. https://doi.org/10.1186/s12864-015-1642-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mao GE, Reuter VE, Cordon-Cardo C, Dalbagni G, Scher HI, DeKernion JB, Zhang ZF, Rao J (2004) Decreased retinoid X receptor-alpha protein expression in basal cells occurs in the early stage of human prostate cancer development. Cancer Epidemiol Biomark Prevent 13(3):383–390

    CAS  Google Scholar 

  33. Dhillon PK, Barry M, Stampfer MJ, Perner S, Fiorentino M, Fornari A, Ma J, Fleet J, Kurth T, Rubin MA, Mucci LA (2009) Aberrant cytoplasmic expression of p63 and prostate cancer mortality. Cancer Epidemiol Biomark Prevent 18 (2):595–600. https://doi.org/10.1158/1055-9965.epi-08-0785

    Article  CAS  Google Scholar 

  34. Higuchi T, Nakamura M, Shimada K, Ishida E, Hirao K, Konishi N (2008) HRK inactivation associated with promoter methylation and LOH in prostate cancer. Prostate 68(1):105–113. https://doi.org/10.1002/pros.20600

    Article  CAS  PubMed  Google Scholar 

  35. Hu X, Chen X, Ping H, Chen Z, Zeng F, Lu G (2005) Immunohistochemical analysis of Omi/HtrA2 expression in prostate cancer and benign prostatic hyperplasia. J Huazhong Univ Sci Technol Med Sci 25(6):671–673

    Article  CAS  Google Scholar 

  36. Wong AK, Chen Y, Lian L, Ha PC, Petersen K, Laity K, Carillo A, Emerson M, Heichman K, Gupte J, Tavtigian SV, Teng DH (1999) Genomic structure, chromosomal location, and mutation analysis of the human CDC14A gene. Genomics 59(2):248–251. https://doi.org/10.1006/geno.1999.5863

    Article  CAS  PubMed  Google Scholar 

  37. Kokontis JM, Lin HP, Jiang SS, Lin CY, Fukuchi J, Hiipakka RA, Chung CJ, Chan TM, Liao S, Chang CH, Chuu CP (2014) Androgen suppresses the proliferation of androgen receptor-positive castration-resistant prostate cancer cells via inhibition of Cdk2, CyclinA, and Skp2. PLoS ONE 9(10):e109170. https://doi.org/10.1371/journal.pone.0109170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Murata T, Takayama K, Urano T, Fujimura T, Ashikari D, Obinata D, Horie-Inoue K, Takahashi S, Ouchi Y, Homma Y, Inoue S (2012) 14-3-3zeta, a novel androgen-responsive gene, is upregulated in prostate cancer and promotes prostate cancer cell proliferation and survival. Clin Cancer Res 18(20):5617–5627. https://doi.org/10.1158/1078-0432.ccr-12-0281

    Article  CAS  PubMed  Google Scholar 

  39. Olsson AY, Feber A, Edwards S, Te Poele R, Giddings I, Merson S, Cooper CS (2007) Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells. Oncogene 26(7):1028–1037. https://doi.org/10.1038/sj.onc.1209854

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would to thank to the medical team of Urology department and pathology anatomy and cytology department, Charles Nicolle Hospital, Tunis, Tunisia. We wish to thank to Rosa Somoza and Teresa Moline for their excellent technical assistance (Pathology Department at Vall d´Hebron Hospital), all members of Dr. LLeonart´s laboratory.

Funding

This work was supported by grants from the Instituto de Salud Carlos III, Grants PI12/01104 and PI15/01262 cofinanced by the European Regional Development Fund (ERDF) (ME LLeonart).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Slah Ouerhani.

Ethics declarations

Conflict of interest

All authors would like to declare that they have no conflict of interest.

Ethics approval

This work is approved by Ethic committee of Charles Nicolle-Tunis-Tunisia.

Informed consent

For this type of retrospective study formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Said, R., Garcia-Mayea, Y., Trabelsi, N. et al. Expression patterns and bioinformatic analysis of miR-1260a and miR-1274a in Prostate Cancer Tunisian patients. Mol Biol Rep 45, 2345–2358 (2018). https://doi.org/10.1007/s11033-018-4399-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-018-4399-x

Keywords

Navigation