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MicroRNA sequencing detects miR-424-5p up-regulation in ovarian cancer stem cells

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Abstract

Cancer stem cells (CSCs) are cancer cells that possess the ability to undergo continuous proliferation and self-renewal. It has been postulated that CSCs are responsible for tumor growth, heterogeneity, invasion, metastasis, and recurrence. MicroRNAs (miRNAs), small non-coding RNAs of approximately 22 nucleotides, are known to be involved in the maintenance of CSCs. To gain insight into the role of miRNAs in CSCs, we investigated the differential expression of miRNAs in ovarian CSCs compared to non-CSCs. Ovarian CSCs were isolated from the human ovarian cancer cell line SK-OV-3 using two ovarian CSC-specific surface markers, CD44 and CD117. The expression levels of miRNAs in CSCs and non-CSCs were estimated by miRNA sequencing. We detected four up-regulated miRNAs (miR-29a-5p, miR-34c-5p, miR-106a-5p, and miR-424-5p) in ovarian CSCs, and miR-424-5p was validated by real-time qPCR. MiR-424-5p target genes were predicted using several validated target databases and computational algorithms. Pathway analysis indicated that most miR-424-5p target genes are involved in cancer-related biological pathways. Overall, these results suggest that miR-424-5p is a potential regulator of CSCs that endows human ovarian tissue with tumorigenic potential and thus represents a potential therapeutic target for human ovarian cancer.

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References

  • Alvero AB, Chen R, Fu HH et al (2009) Molecular phenotyping of human ovarian cancer stem cells unravel the mechanisms for repair and chemo-resistance. Cell Cycle 8:158–166

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ashburner M, Ball CA, Blake JA et al (2000) Gene Ontology: tool for the unification of biology. Nat Genet 25:25–29

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bapat SA (2010) Human ovarian cancer stem cells. Reproduction 140:33–41

    Article  CAS  PubMed  Google Scholar 

  • Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Zhang Y, Wang J, Chen J, Yang C, Cai K, Wang X, Shi F, Dou J (2013a) MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117 + CD44 + ovarian cancer stem cells by regulating epithelial-mesenchymal transition. J Ovarian Res 6:50

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen J, Wang J, Chen D, Yang J, Yang C, Zhang Y, Zhang H, Dou J (2013b) Evaluation of characteristics of CD44 + CD117 + ovarian cancer stem cells in three dimensional basement membrane extract scaffold versus two dimensional monocultures. BMC Cell Biol 14:7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Deiters A (2010) Small Molecule Modifiers of the microRNA and RNA Interference Pathway. AAPS J 12:51–60

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:R60

    Article  PubMed Central  Google Scholar 

  • Di Leva G, Croce CM (2013) The Role of microRNAs in the Tumorigenesis of Ovarian Cancer. Front Oncol 3:153

    PubMed Central  PubMed  Google Scholar 

  • He L, Hannon GJ (2004) Micrornas: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  CAS  PubMed  Google Scholar 

  • Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  CAS  Google Scholar 

  • Iorio MV, Visone R, Di Leva G et al (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67:8699–8707

    Article  CAS  PubMed  Google Scholar 

  • Kanehisa M, Goto S (2000) KEGG: kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 28:27–30

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M (2006) From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 34:D354–D357

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kreso A, Dick JE (2014) Evolution of the Cancer Stem Cell Model. Cell Stem Cell 14:275–291

    Article  CAS  PubMed  Google Scholar 

  • Li F, Tiede B, Massague J, Kang YB (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Tang DG (2011) MicroRNA Regulation of Cancer Stem Cells. Cancer Res 71:5950–5954

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Luo LJ, Zeng JF, Liang B, Zhao Z, Sun LL, Cao DY, Yang JX, Shen K (2011) Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol 91:596–602

    Article  CAS  PubMed  Google Scholar 

  • Oneyama C, Kito Y, Asai R et al (2013) MiR-424/503-mediated Rictor upregulation promotes tumor progression. PLOS One 8:e80300

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Papagiannakopoulos T, Kosik KS (2008) MicroRNAs: regulators of oncogenesis and stemness. BMC Med 6:15

    Article  PubMed Central  PubMed  Google Scholar 

  • Park YT, Jeong JY, Lee MJ, Kim KI, Kim TH, Kwon YD, Lee C, Kim OJ, An HJ (2013) MicroRNAs overexpressed in ovarian ALDH1-positive cells are associated with chemoresistance. J Ovarian Res 6:18

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10:57–63

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zaman MS, Maher DM, Khan S, Jaggi M, Chauhan SC (2012) Current status and implications of microRNAs in ovarian cancer diagnosis and therapy. J Ovarian Res 5:13

    Article  Google Scholar 

  • Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang THM, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68:4311–4320

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang D, Shi Z, Li M, Mi J (2014) Hypoxia-induced miR-424 decreases tumor sensitivity to chemotherapy by inhibiting apoptosis. Cell Death Dis 5:6

    Google Scholar 

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Acknowledgments

This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012M3A9D1054534), the Hallym University Specialization Fund (HRF-S-11), and an intramural grant from the Korea Institute of Science and Technology (2z04381).

Conflict of interest

The authors declare no conflicts of interest.

Ethical statement

In this study, human ovarian cancer cells were obtained from the commercially available human ovary adenocarcinoma (ATCC® HTB-77™). This study was approved by Hallym University Institutional Review Board (HIRB).

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    Authors and Affiliations

    1. Natural Products Research Center, KIST Gangneung Institute of Natural Products, Gangneung, Gangwon-do, 210-340, Republic of Korea

      Ji Ho Yun, In Su Ha, Ji Min Shin & Chu Won Nho

    2. Department of Life Science, Sogang University, Seoul, 121-741, Republic of Korea

      Ji Ho Yun, Jung Hoon Kim & Jungho Kim

    3. Department of Biomedical Science, Hallym University, Chuncheon, Gangwon-do, 200-702, Republic of Korea

      Jisun Lim & Yoon Shin Cho

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    1. Ji Ho Yun
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    2. Jisun Lim
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    Correspondence to Chu Won Nho or Yoon Shin Cho.

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    Ji Ho Yun and Jisun Lim have contributed equally to co-first authors.

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    Yun, J.H., Lim, J., Ha, I.S. et al. MicroRNA sequencing detects miR-424-5p up-regulation in ovarian cancer stem cells. Genes Genom 37, 737–742 (2015). https://doi.org/10.1007/s13258-015-0299-9

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    • DOI: https://doi.org/10.1007/s13258-015-0299-9

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