RETRACTED: MiR-139-5p inhibits HGTD-P and regulates neuronal apoptosis induced by hypoxia‚Äìischemia in neonatal rats
Authors: Jinlin Wu
Chunlei Yang
Fengyan Zhao
Junyan Liu
Dapeng Wei
Yi Qu
Dapeng Chen
Donna M Ferriero
Dezhi Mu
Journal: Neurobiology of Disease (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: 3‚Ä?untranslated regions; 3‚Ä≤UTR; AI; AIF; Apoptosis
Affiliations: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, 610041 Chengdu, Sichuan, China. Electronic address: ., Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China., Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, 610041 Chengdu, Sichuan, China., West China Medical Center, Sichuan University, 610041 Chengdu, Sichuan, China., Department of Pediatrics and Neurology, University of California, San Francisco, CA 94143, USA., Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, 610041 Chengdu, Sichuan, China; Department of Pediatrics and Neurology, University of California, San Francisco, CA 94143, USA. Electronic address: .

Abstract:  Human growth transformation dependent protein (HGTD-P) is a newly identified protein that promotes neuronal apoptosis in hypoxia-ischemia brain damage (HIBD) in neonatal rats. However, the mechanisms regulating HGTD-P expression are not clear. Here we describe microRNAs targeted to HGTD-P and examine their effects on regulating neuronal apoptosis in HIBD. We use samples from cultured neurons after oxygen-glucose deprivation (OGD) and postnatal day 10 rat brains after hypoxia-ischemia (HI). RT-PCR, Western blotting, and immunostaining are used to detect the expression of HGTD-P and cleaved caspase 3, as well as real-time PCR detects microRNA expression. MicroRNA agomir is used to inhibit the expression of HGTD-P, and DAPI, TUNEL, and TTC staining are employed to detect cell apoptosis and brain damage. Moreover, in vitro processing assay is used to examine the mechanism by which HI down-regulates miR-139-5p expression. We found that miR-139-5p is down-regulated in neurons and rat brains after HI treatment. The expression pattern of miR-139-5p correlates inversely with that of HGTD-P. Furthermore, miR-139-5p agomir inhibits neuronal apoptosis and attenuates HIBD, which is concurrent with down-regulation of HGTD-P. Moreover, pre-miR-139 processing activity decreases in extracts from OGD neurons, and OGD neuronal extracts attenuates the processing of pre-miR-139 by Dicer. In conclusion, HI induces inhibitors which block the processing step of pre-miR-139, resulting in the down-regulation of mature miR-139-5p. The down-regulation of miR-139-5p plays a critical role in the up-regulation of HGTD-P expression. MiR-139-5p agomir attenuates brain damage when used 12h after HI, providing a longer therapeutic window than anti-apoptosis compounds currently available. 

Retracted: Yes

PubPeer comments:
 Figure 2A. * Green arrows: Lanes  24 and 36 in the HGTD-P panel appear to look similar.  , 
 Figure 2B. * The bands in the HGTD-P appear to be surrounded by sharp rectangular background transitions. * Red arrows: the bands in the beta-actin panel all look very similar to each other.  , 
 Figure 3C appears to show some repetitive elements. Boxes of the same color draw attention to cells that look similar.  , 
 Figure 3D and 5B appear to share many features. Square boxes of the same color denote panels that look similar to each other, albeit rotated or stretched differently. Rounded boxes of the same color denote cells or groups of cells that look similar to each other.  , 
 Dear Dr. Bik, Thank you very much for pointing out the mistakes of the figurers. I am the co-corresponding author of the paper. I have contacted the first author and the first corresponding author to carefully check the figures and will response to you as soon as possible. Sincerely, Dezhi Mu , 
 Dear Dr. Bik, Iu2019m the first author of the paper. Thank you very much for helping us to find out the mistakes in this paper. We are now checking the original data, especially the figures from the collaborating units. We are very sorry for these mistakes. , 
 Retracted [3 March 2022] . -------------------- This article has been retracted at the request of the Authors. Dr. Elisabeth Bik raised concerns about the article on PubPeer [https: pubpeer.com publications 67D613FA97B87C373F239931962126]. In Fig. 2A. Lanes 24 and 36 in the HGTD-P panel appear to look similar. In Fig. 2B. The bands in the HGTD-P appear to be surrounded by sharp rectangular background transitions and the bands in the beta-actin panel all look very similar to each other. Fig. 3C appears to show some repetitive elements. Figs. 3D and 5B appear to contain some similar or duplicated features. The authors declare that they did not modify the figures deliberately, that they have repeated the experiments and that the experiments are reproducible, and that the above concerns do not seem to affect the conclusion of the article. ,