MicroRNA-185-5p restores glucocorticoid sensitivity by suppressing the mammalian target of rapamycin complex (mTORC) signaling pathway to enhance glucocorticoid receptor autoregulation

Abstract

Overexpression of microRNA-185-5p (miR-185-5p) in glucocorticoid (GC)-sensitive acute lymphoblastic leukemia (ALL) was identified using a microarray and reverse transcription polymerase chain reaction and was further confirmed in ALL cell lines. A reporter assay confirmed that the Rictor-one component of mammalian target of rapamycin complex 2 (mTORC2) is a target of miR-185-5p. Decreased mTORC activity was also confirmed in GC-sensitive patients. Overexpression of miR-185-5p significantly enhanced GC sensitivity in CEM-C1 cells (GC resistance) by increasing the rate of cell apoptosis and cycle arrest, and decreasing cell survival, accompanied by a decrease in mTORC activity and an increase in GC-induced glucocorticoid receptor (GR) expression. Rapamycin, an mTORC1 inhibitor, showed similar effects to miR-185-5p. These results demonstrated that miR-185-5p enhances GC sensitivity via suppression of mTORC activity by enhancing GR autoupregulation and that miR-185-5p is a potential target for the diagnosis and reversion of GC resistance.

Keywords:

• MiR-185-5p
• glucocorticoid resistance
• mTORC
• acute lymphoblastic leukemia

Acknowledgements

We thank Professor Zhigui Ma for kindly providing CEM - C7 cell lines. This work was supported by the National Natural Science Foundation of China [grant number 81101316].

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2017.1296143

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81101316].