title: Pseudogene PTENP1 Functions as a Competing Endogenous RNA (ceRNA) to Regulate PTEN Expression by Sponging miR-499-5p.
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.
authors.affiliation: Nanjing University of Chinese Medicine, Second Medical School, Department of Rehabilitation Medicine, Nanjing, 210023, China. Wanglei150306@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Zun
authors.initials: Z
authors.lastname: Wang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Ai
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Cao
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Pan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D059305:Diet, High-Fat; D017930:Genes, Reporter; D006003:Glycogen / Q000096:biosynthesis; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011544:Pseudogenes / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D007328:Insulin; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D006003:Glycogen; D038341:Glycogen Synthase Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse