MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT activation

Lixia Guo, Jingyu Wang, Ping Yang, Qiang Lu, Ting Zhang, Yanan D Yang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

MicroRNA-200 (miR-200) has emerged as a regulator of the PI3K/AKT pathway and cancer cell growth. It was reported that miR-200 can activate PI3K/AKT by targeting FOG2 (friend of GATA 2), which directly binds to the p85α regulatory subunit of PI3K. We found that miR-200 was elevated in early stage lung adenocarcinomas when compared with normal lung tissues, and the expression of miR-200 promoted the tumor spheroid growth of lung adenocarcinoma cells. We show that AKT activation was essential for such oncogenic action of miR-200. However, depletion of FOG2 had little effect on AKT activation. By performing a reverse-phase protein array, we found that miR-200 not only activated AKT but also concomitantly inactivated S6K and increased IRS-1, an S6K substrate that is increased on S6K inactivation. Depletion of IRS-1 partially inhibited the miR-200-dependent AKT activation. Taken together, our results suggest that miR-200 may activate AKT in lung adenocarcinoma cells through a FOG2-independent mechanism involving IRS-1. Our findings also provide evidence that increased miR-200 expression may contribute to early lung tumorigenesis and that AKT inhibitors may be useful for the treatment of miR-200-dependent tumor cell growth.

Original languageEnglish (US)
Pages (from-to)720-725
Number of pages6
JournalIUBMB Life
Volume67
Issue number9
DOIs
StatePublished - Sep 1 2015

Fingerprint

Cell growth
MicroRNAs
Lung Neoplasms
Chemical activation
Growth
Phosphatidylinositol 3-Kinases
Tumors
Neoplasms
Lung
Protein Array Analysis
Carcinogenesis
Tissue

Keywords

  • AKT
  • lung cancer
  • microRNA-200
  • signaling

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics

Cite this

MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT activation. / Guo, Lixia; Wang, Jingyu; Yang, Ping; Lu, Qiang; Zhang, Ting; Yang, Yanan D.

In: IUBMB Life, Vol. 67, No. 9, 01.09.2015, p. 720-725.

Research output: Contribution to journalArticle

Guo, Lixia ; Wang, Jingyu ; Yang, Ping ; Lu, Qiang ; Zhang, Ting ; Yang, Yanan D. / MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT activation. In: IUBMB Life. 2015 ; Vol. 67, No. 9. pp. 720-725.
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