International Journal of Molecular Sciences (May 2016)

EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6

  • Li Zhou,
  • Jin Hao,
  • Yue Yuan,
  • Rui Peng,
  • Honglian Wang,
  • Dongsheng Ni,
  • Yuping Gu,
  • Liyuan Huang,
  • Zhaomin Mao,
  • Zhongshi Lyu,
  • Yao Du,
  • Zhicheng Liu,
  • Yiman Li,
  • Pan Ju,
  • Yaoshui Long,
  • Jianing Liu,
  • Qin Zhou

DOI
https://doi.org/10.3390/ijms17060811
Journal volume & issue
Vol. 17, no. 6
p. 811

Abstract

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Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy.

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