Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells

Penn Muluhngwi, Abirami Krishna, Stephany L. Vittitow, Joshua T. Napier, Kirsten M. Richardson, Mackenzie Ellis, Justin L. Mott, Carolyn M. Klinge

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Endocrine-resistance develops in ∼40% of breast cancer patients after tamoxifen (TAM) therapy. Although microRNAs are dysregulated in breast cancer, their contribution to endocrine-resistance is not yet understood. Previous microarray analysis identified miR-29a and miR-29b-1 as repressed by TAM in MCF-7 endocrine-sensitive breast cancer cells but stimulated by TAM in LY2 endocrine-resistant breast cancer cells. Here we examined the mechanism for the differential regulation of these miRs by TAM in MCF-7 versus TAM-resistant LY2 and LCC9 breast cancer cells and the functional role of these microRNAs in these cells. Knockdown studies revealed that ERα is responsible for TAM regulation of miR-29b-1/a transcription. We also demonstrated that transient overexpression of miR-29b-1/a decreased MCF-7, LCC9, and LY2 proliferation and inhibited LY2 cell migration and colony formation but did not sensitize LCC9 or LY2 cells to TAM. Furthermore, TAM reduced DICER1 mRNA and protein in LY2 cells, a known target of miR-29. Supporting this observation, anti-miR-29b-1 or anti-miR-29a inhibited the suppression of DICER by 4-OHT. These results suggest miR-29b-1/a has tumor suppressor activity in TAM-resistant cells and does not appear to play a role in mediating TAM resistance.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalCancer Letters
Volume388
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant R01 CA138410 and in part by a grant from the University of Louisville School of Medicine to C.M.K.; by National Institutes of Health T35 DK072923 to C.M.K. that supported the research training of medical students A.K. and J.T.N.; S.L.V. was supported by a fellowship from the University of Louisville Vice President for Research and Innovation's Summer Research Opportunity Program (SROP).

Publisher Copyright:
© 2016 Elsevier Ireland Ltd

Keywords

  • Breast cancer
  • Endocrine-resistance
  • Estrogen receptor
  • miRNA-29a
  • miRNA-29b-1
  • Tamoxifen

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