2Nanjing University Medical School, Nanjing Drum Tower Hospital, Department of Cardiology, 210093 Nanjing, China
3Affiliated Jiangning Hospital of Nanjing Medical University, Department of Rehabilitation Medicine, 211100 Nanjing, China; E-mail: email@example.com
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
Received February 3, 2016; Revision received March 22, 2016
Increasing evidence has shown that pseudogenes can widely regulate gene expression. However, little is known about the specific role of PTENP1 and miR-499-5p in insulin resistance. The relative transcription level of PTENP1 was examined in db/db mice and high fat diet (HFD)-fed mice by real-time PCR. To explore the effect of PTENP1 on insulin resistance, adenovirus overexpressing or inhibiting vectors were injected through the tail vein. Bioinformatics predictions and a luciferase reporter assay were used to explore the interaction between PTENP1 and miR-499-5p. The relative transcription level of PTENP1 was largely enhanced in db/db mice and HFD-fed mice. Furthermore, the overexpression of PTENP1 resulted in impaired Akt/GSK activation as well as glycogen synthesis, while PTENP1 inhibition led to the improved activation of Akt/GSK and enhanced glycogen contents. More importantly, PTENP1 could directly bind miR-499-5p, thereby becoming a sink for miR-499-5p. PTENP1 overexpression results in the impairment of the insulin-signaling pathway and may function as a competing endogenous RNA for miR-499-5p, thereby contributing to insulin resistance.
KEY WORDS: PTENP1, ceRNA, PTEN, miR-499-5p