Downregulation of APRIN expression increases cancer cell proliferation via an interleukin-6/STAT3/cyclin D axis

Min Shik Sohn, Miae Kang, Seong Man Kang, Sangwoo Bae

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


APRIN is a putative tumor suppressor whose expression is low in a variety of cancer cells. While decreased expression of APRIN leads to increased cell proliferation, unfavorable diagnosis or metastases in various cancer types, there is limited knowledge on the cellular mechanism of APRIN in cellular responses. The effect of APRIN deple- tion on cancer cell proliferation was examined in the present study, and the IL-6/STAT3/cyclin D axis was identified as a novel regulatory mechanism. Stable depletion of APRIN in cancer cells resulted in increased cell proliferation. Cytokine array analysis of the cells revealed that downregulation of APRIN induced secretion of interleukin-6 (IL-6) with corresponding activation of STAT3, a downstream intracel- lular mediator. Levels of cyclin D1 were increased in cells with APRIN depletion and cyclin D1 expression was associ- ated with increased STAT3 binding on cyclin D1 promoter sequence; assessed by chromatin immunoprecipitation assay. The addition of an IL-6 neutralizing antibody P620 to the cell culture attenuated STAT3 activation and cyclin D1 expression in APRIN-depleted cells with corresponding decrease in cell proliferation. These experiments suggest that APRIN regu- lates cancer cell proliferation via an IL-6/STAT3/cyclin D axis and that targeting this axis in APRIN-associated cancer might provide a novel therapeutic approach.

Original languageEnglish
JournalOncology Letters
Issue number1
Publication statusPublished - 2021 Jan

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Institute of Radiological and Medical Sciences (grant no. 50531‑2020) funded by Ministry of Science and ICT, Republic of Korea.

Publisher Copyright:
© 2021 Spandidos Publications. All rights reserved.


  • Cancer cell proliferation
  • Cyclin D1
  • Interleukin-6
  • STAT3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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