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 language | English (US) |
---|---|
Pages (from-to) | 720-725 |
Number of pages | 6 |
Journal | IUBMB Life |
Volume | 67 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2015 |
Keywords
- AKT
- lung cancer
- microRNA-200
- signaling
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
- Clinical Biochemistry
- Cell Biology