Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of let-7a in breast cancer cells

PLoS One. 2013 Dec 11;8(12):e83083. doi: 10.1371/journal.pone.0083083. eCollection 2013.

Abstract

The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplastic Stem Cells / metabolism*
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics

Substances

  • Lin28A protein, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human

Grants and funding

This work was supported by grants from Guangdong Natural Science Funds for Distinguished Young Scholar (S20120011199), Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (121042), Program for New Century Excellent Talents in University of Ministry of Education of China (NCET-09-0816), Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD, 81000-3149001), Foundation for the Young Teachers in the Higher Education Institutions of China (20110171120082), Natural Science Foundation of China (81172524, 81072178, 81272894, 81102022), Science Foundation of Guangdong Province (S2012030006287) and Translational medicine public platform of Guangdong Province(4202037). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.