Skip to main content
Log in

miR-107 targets cyclin-dependent kinase 6 expression, induces cell cycle G1 arrest and inhibits invasion in gastric cancer cells

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) have emerged as post-transcriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Recently, cyclin-dependent kinase 6 (CDK6) is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. We have identified miR-107 as a potential regulator of CDK6 expression. A bioinformatics search revealed a putative target site for miR-107 within the CDK6 3′ untranslated region. Expression of miR-107 in gastric cancer cell lines was found inversely correlated with CDK6 expression. miR-107 could significantly suppress CDK6 3′ UTR luciferase reporter activity, and this effect was not detectable when the putative 3′ UTR target site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-107 reduced both mRNA and protein expression levels of CDK6, inhibited proliferation, induced G1 cell cycle arrest, and blocked invasion of the gastric cancer cells. Our results suggest that miR-107 may have a tumor suppressor function by directly targeting CDK6 to inhibit the proliferation and invasion activities of gastric cancer cells.

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
Fig. 4

Similar content being viewed by others

References

  1. Liu SP, Fu RH, Yu HH, et al. MicroRNAs regulation modulated self-renewal and lineage differentiation of stem cells. Cell Transplant. 2009;18(9):1039–45.

    Article  PubMed  Google Scholar 

  2. Lujambio A, Calin GA, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. 2008;105(36):13556–61.

    Article  PubMed  CAS  Google Scholar 

  3. Huang YW, Liu JC, Deatherage DE, et al. Epigenetic repression of microRNA-129–2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res. 2009;69(23):9038–46.

    Article  PubMed  CAS  Google Scholar 

  4. Matushansky I, Radparvar F, Skoultchi AI. CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells. Oncogene. 2003;22(27):4143–9.

    Article  PubMed  CAS  Google Scholar 

  5. Tomita T. Cyclin-dependent kinase (cdk6) and p16 in pancreatic endocrine neoplasms. Pathology. 2004;36(6):566–70.

    Article  PubMed  CAS  Google Scholar 

  6. Matushansky I, Radparvar F, Skoultchi AI. Reprogramming leukemic cells to terminal differentiation by inhibiting specific cyclin-dependent kinases in G1. Proc Natl Acad Sci USA. 2000;97(26):14317–22.

    Article  PubMed  CAS  Google Scholar 

  7. Lee KH, Lotterman C, Karikari C, et al. Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer. Pancreatology. 2009;9(3):293–301.

    Article  PubMed  CAS  Google Scholar 

  8. Pierson J, Hostager B, Fan R, Vibhakar R. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol. 2008;90(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  9. Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci. 2005;30(11):630–41.

    Article  PubMed  CAS  Google Scholar 

  10. Landis MW, Pawlyk BS, Li T, Sicinski P, Hinds PW. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell. 2006;9(1):13–22.

    Article  PubMed  CAS  Google Scholar 

  11. Mendrzyk F, Radlwimmer B, Joos S, et al. Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma. J Clin Oncol. 2005;23(34):8853–62.

    Article  PubMed  CAS  Google Scholar 

  12. Shen R, Pan S, Qi S, Lin X, Cheng S. Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer. Biochem Biophys Res Commun. 2010;394(4):1047–52.

    Article  PubMed  CAS  Google Scholar 

  13. Liu M, Lang N, Qiu M, et al. miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells. Int J Cancer.

  14. Noren Hooten N, Abdelmohsen K, Gorospe M, Ejiogu N, Zonderman AB, Evans MK. microRNA expression patterns reveal differential expression of target genes with age. PloS One. 2010;5(5):e10724.

    Article  PubMed  Google Scholar 

  15. Garzon R, Pichiorri F, Palumbo T, et al. MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene. 2007;26(28):4148–57.

    Article  PubMed  CAS  Google Scholar 

  16. Takahashi Y, Forrest AR, Maeno E, Hashimoto T, Daub CO, Yasuda J. MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines. PloS one. 2009;4(8):e6677.

    Article  PubMed  Google Scholar 

  17. Roldo C, Missiaglia E, Hagan JP, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006;24(29):4677–84.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Shanghai Municipal Natural Science Foundation (Grand no: 10ZR1426300).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yunlin Wu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 46 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, L., Xie, Y., Zhang, H. et al. miR-107 targets cyclin-dependent kinase 6 expression, induces cell cycle G1 arrest and inhibits invasion in gastric cancer cells. Med Oncol 29, 856–863 (2012). https://doi.org/10.1007/s12032-011-9823-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-9823-1

Keywords

Navigation