Downregulated expression of microRNA-329 inhibits apoptosis of nigral dopaminergic neurons by regulating CDKN2D expression via the FoxO3a signaling pathway in rats with Parkinson's disease
Authors: Qing-Shan Yang
Yi-Nan Zhang
Yuan-Yuan Liu
Journal: Journal of Cellular Physiology (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Forkhead box O3a signaling pathway; Parkinson's disease; apoptosis; cyclin dependent kinase inhibitor 2D; microRNA-329
Affiliations: Department of Neurology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, P.R. China., Department of Radiation Oncology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, P.R. China.

Abstract:  Parkinson's disease (PD) is a common neurodegenerative disorder due to the loss of dopaminergic neurons in the substantia nigra. This study focuses on the effect of microRNA-329 (miR-329) on nigral dopaminergic neurons in a rat model of PD via the FoxO3a signaling pathway by binding to CDKN2D. Brain tissues from the substantia nigra were taken from the rats in two groups. TUNEL staining was used to observe tyrosine hydroxylase (TH)-positive neurons. Nigral dopaminergic neurons were randomized into the normal, blank, negative control (NC), miR-329 mimics, miR-329 inhibitors, small interfering (siRNA)-CDKN2D, and miR-329 inhibitors + siRNA-CDKN2D groups. Expressions of miR-329, CDKN2D, FoxO3a, AKT, caspase-3 and Bcl-2 were determined using RT-qPCR and western blotting. Apoptosis rate of nigral dopaminergic neurons in 7 groups was determined by flow cytometry. Compared with the blank and NC groups, the miR-329 mimics group showed increased miR-329 and caspase-3 expressions as well as decreased expressions of CDKN2D, FoxO3a, AKT, and Bcl-2, the siRNA-CDKN2D group indicated enhanced expressions of caspase-3 and declined expressions of CDKN2D, FoxO3a, AKT, and Bcl-2, and the miR-329 inhibitors group revealed decreased miR-329 and caspase-3 expressions and increased expressions of CDKN2D, FoxO3a, AKT, and Bcl-2. The apoptosis rate of nigral dopaminergic neurons was significantly increased in the miR-329 mimics and siRNA-CDKN2D groups, but was decreased in the miR-329 inhibitors group. Our data suggested that downregulated miR-329 could inhibit apoptosis of nigral dopaminergic neurons in a rat model of PD by upregulating the expression of CDKN2D via the activation of the FoxO3a signaling pathway. 

Retracted: Yes

PubPeer comments:
 FIGURE 10(a)  Up-regulated miR-329 and down-regulated CDKN2D accelerated the apoptosis of nigral dopaminergic neurons measured by flow cytometry. (a) Apoptosis mapping of nigral dopaminergic neurons in seven groups . I have marked some areas where cells are repeated between separate experiments. ![file] , 
 FIGURE 5(b)  Protein expressions of CDKN2D, FoxO3a, p-FoxO3a, AKT, p-AKT, and Bcl-2 were reduced but the protein expression of caspase-3 was enhanced in the PD group compared with the normal group detected by western blot analysis ... (b) protein bands in the normal and PD groups observed after Western blotting ; and 9(c)  miR-329 could down-regulate the mRNA expression of CDKN2D and FoxO3a in nigral dopaminergic neurons after transfection detected by western blot. ... (c) protein bands in seven groups observed after western blotting . ![file] Both loading controls exhibit a bubble under one of the blobs, suggesting that the former control is a detail of the latter one, despite the different conditions. In fact the entire loading control (with the distinctive bubble and the eye in another blob) recur through this whole oeuvre. , 
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 15 May 2018 in Wiley Online Library has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,