c-Fos-dependent miR-22 targets MDC1 and regulates DNA repair in terminally differentiated cells

Jung Hee Lee, Seon Joo Park, Seok Won Kim, Gurusamy Hariharasudhan, Sung Mi Jung, Semo Jun, Jeongsik Yong, Ho Jin You

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Terminally differentiated cells have a reduced capacity to repair double-stranded breaks (DSB) in DNA, however, the underlying molecular mechanism remains unclear. Here, we show that miR-22 is upregulated during postmitotic differentiation of human breast MCF-7 cells, hematopoietic HL60 and K562 cells. Increased expression of miR-22 in differentiated cells was associated with decreased expression of MDC1, a protein that plays a key role in the response to DSBs. This downregulation of MDC1 was accompanied by reduced DSB repair, impaired recruitment of the protein to the site of DNA damage following IR. Conversely, inhibiting miR-22 enhanced MDC1 protein levels, recovered MDC1 foci, fully rescued DSB repair in terminally differentiated cells. Moreover, MDC1 levels, IR-induced MDC1 foci, and the efficiency of DSB repair were fully rescued by siRNA-mediated knockdown of c-Fos in differentiated cells. These findings indicate that the c-Fos/miR-22/MDC1 axis plays a relevant role in DNA repair in terminally differentiated cells, which may facilitate our understanding of molecular mechanism underlying the downregulating DNA repair in differentiated cells.

Original languageEnglish (US)
Pages (from-to)48204-48221
Number of pages18
JournalOncotarget
Volume8
Issue number29
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
We thank all laboratory members that provided input and advice on this project.This work is supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (NRF-2015R1A5A2009070, 2017R1A2B2007557).

Publisher Copyright:
© Lee et al.

Keywords

  • C-Fos
  • DNA repair
  • Differentiation
  • MDC1
  • MiR-22

Fingerprint

Dive into the research topics of 'c-Fos-dependent miR-22 targets MDC1 and regulates DNA repair in terminally differentiated cells'. Together they form a unique fingerprint.

Cite this