Abstract
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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Abbreviations
- ceRNA:
-
competing endogenous RNA
- db/db mouse:
-
mouse with db/db mutation, a model for diabetic dyslipidemia
- GFP:
-
green fluorescent protein
- GTT:
-
glucose tolerance test
- HFD:
-
high fat diet
- ITT:
-
insulin tolerance test
- lncRNAs:
-
long noncoding RNAs
- miRNA (miR):
-
microRNAs
- PTENP1:
-
phosphatase and tensin homolog pseudogene 1
- 3′-UTR:
-
3′-untranslated region
- WT:
-
wild-type
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Published in Russian in Biokhimiya, 2016, Vol. 81, No. 7, pp. 971-981.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-029, April 24, 2016.
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Wang, L., Zhang, N., Wang, Z. et al. Pseudogene PTENP1 functions as a competing endogenous RNA (ceRNA) to regulate PTEN expression by sponging miR-499-5p. Biochemistry Moscow 81, 739–747 (2016). https://doi.org/10.1134/S0006297916070105
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DOI: https://doi.org/10.1134/S0006297916070105