Pseudogene PTENP1 Functions as a Competing Endogenous RNA (ceRNA) to Regulate PTEN Expression by Sponging miR-499-5p

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Lei Wang^1#*, Ning Zhang^2#, Zun Wang¹, Dong-mei Ai¹, Zhen-yu Cao¹, and Hua-ping Pan^3*

¹Nanjing University of Chinese Medicine, Second Medical School, Department of Rehabilitation Medicine, 210023 Nanjing, China; E-mail: Wanglei150306@163.com

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: panhuaping160411@163.com

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received February 3, 2016; Revision received March 22, 2016

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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.

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KEY WORDS: PTENP1, ceRNA, PTEN, miR-499-5p

DOI: 10.1134/S0006297916070105

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