Expression patterns and bioinformatic analysis of miR-1260a and miR-1274a in Prostate Cancer Tunisian patients
- 42 Downloads
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.
KeywordsMiR-1260 MiR-1274a Over-expression Epigenetic Prostate cancer Tunisia
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.
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).
Compliance with ethical standards
Conflict of interest
All authors would like to declare that they have no conflict of interest.
This work is approved by Ethic committee of Charles Nicolle-Tunis-Tunisia.
For this type of retrospective study formal consent is not required.
- 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedPubMedCentralGoogle 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):383–390Google 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 CrossRefGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle Scholar