Breast Cancer Research and Treatment

, Volume 126, Issue 3, pp 687–694 | Cite as

Let-7a regulation of insulin-like growth factors in breast cancer

  • Lingeng Lu
  • Dionyssios Katsaros
  • Yong Zhu
  • Aaron Hoffman
  • Scarampi Luca
  • Canuto Emilie Marion
  • Lina Mu
  • Harvey Risch
  • Herbert Yu


Expression of certain microRNA genes is regulated by DNA methylation, which in turn affects the activities of their downstream molecules. Our previous study showed that methylated let-7a-3 was associated with low IGF-II expression and favorable prognosis of ovarian cancer. The roles of let-7a-3 methylation in breast cancer and in regulation of IGF expression in the tumor are still unknown. Let-7a-3 methylation, IGF mRNAs, and peptides were analyzed in 348 breast cancer samples using quantitative methylation-specific PCR, qRT-PCR, and ELISA, respectively. The associations of let-7a-3 methylation with IGFs, disease features, and patient survivals were analyzed. In vitro experiments were performed using HeLa cells transfected with let-7a precursors to assess the effect of let-7a on IGF expression. Let-7a-3 methylation was detected frequently in breast cancer. An inverse correlation between let-7a-3 methylation and IGF expression was observed in breast cancer, which was similar to that seen in ovarian cancer. Our in vitro experiment showed that let-7a could increase IGF expression in cancer cells which had low endogenous let-7a. Let-7a-3 methylation was also found to be associated with high grade tumors and ER- or PR-negative cancer. However, let-7a-3 methylation was not associated with disease-free survival or overall survival of breast cancer patients. The study provides further evidence in support of the notion that epigenetic regulation of let-7a-3 may affect the actions of IGFs in cancer. Let-7a may up-regulate the expression of IGFs in cancer cells, which is different from its inhibitory effects on other oncogenes.


Let-7a-3 methylation IGFs Breast cancer Epigenetics 


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Lingeng Lu
    • 1
  • Dionyssios Katsaros
    • 2
  • Yong Zhu
    • 1
  • Aaron Hoffman
    • 1
  • Scarampi Luca
    • 2
  • Canuto Emilie Marion
    • 2
  • Lina Mu
    • 3
  • Harvey Risch
    • 1
  • Herbert Yu
    • 1
  1. 1.Department of Epidemiology and Public HealthYale Cancer Center, Yale University School of MedicineNew HavenUSA
  2. 2.Department of Obstetrics and GynecologyGynecologic Oncology and Breast Cancer Unit, University of TurinTurinItaly
  3. 3.Department of Social and Preventive MedicineSchool of Public Health and Health Professions, University at Buffalo, The State University of New YorkBuffaloUSA

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