MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α
Authors: Xin-Yi Wang
You-Zhi Xu
Rui-Qing Deng
Fang Ni
Guo Qiang
Ming-Zhen Yang
Peng Yang
Li Chen
Si-Ying Wang
Hua Zhao
Dan-Lei Chen
Zhi-Jun Chen
Li-Xin Kan
Journal: Molecular Cancer (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNAs; miR-362-5p; oncogene; chronic myeloid leukaemia; CML
Affiliations: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. ., Department of Transfusion, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China. ., Department of Haematology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China. ., Department of Clinical Medicine, Anhui Medical University, Hefei, Anhui, 230032, PR China. .

Abstract:  Background: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. Methods: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. Results: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. Conclusion: miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets. 

Retracted: Yes

PubPeer comments:
 Fig. 3A has an overlap between 2 images. The overlap involves some rotation. ![file] , 
 Dear Dr. Tulipa Fosteriana, Thanks for point the error! We have been carefully checked the original paper data. During the preparation of figures submitted in the original manuscript, we inadvertently provided an incorrect image for Figure 3A. In the Figure 3A: the transwell migratory assays images of BV173 were correct, the images of K562 group were incorrect, and the percentage in the right group was correct, the updated version is with correct images. The change did not affect overall conclusion and we have applied for correction. Itu2019s in process. The correct Figure 3A is attached below. We sincerely apologized for this unintentional error made before manuscript submission, but we failed to catch at submission and subsequent review and publication steps. We apologize for this mistake due to our carelessness. Best wishes, Peng Yang ![file] , 
 Dear Manager Thank you very much for pointing out the problems in this article. I found the first author, carefully checked the original experimental results, and carefully re combed and checked the article. I found that the problem you raised about fig 3A does exist. At the same time, I found that the image of K562 inhibitor Ctrl in Fig 3a is not the original experimental results, and the bv173 and K562 Flow cytometry spots in Fig 2D are exactly the same. After examining the original experimental results, it was found that the pictures of the three repeated experimental results in each experiment were real, but the bv173 inhibitor group did not know why there was one more picture. We will contact the editorial office for correction and attach the original experimental results with the emailuff08migration pictures saved as .tif, we will upload soonuff09. ![file] ![file] , 
 #1 The original issues may be more extensive. Difficult to understand how these could be errors, given the deliberate resizing, rotation, and recoloring that appears to have occurred. I will alert the journal to this thread. *** ![file] , 
 #1 and #4 Let me chime in with a demo of how the green boxes overlap Figure 3A was questioned by #1 and a  corrected version was provided by the author in #2. Figure 3B, which was not originally questioned by #1, was found having an overlapped area by #4. The demo shows how superimposing a scaled-down semi-transparent copy of Figure 3B BV173-Inhibitor-ctrl (invasion essay) overlays almost perfectly with Figure 3A BV173-Inhibitor-ctrl migration essay. I agree with #4, it is beyond my imagination how scaling + rotation + cropping + color-brightness adjustment could have been achieved accidentally. Please go ahead reporting to the journal, I m with you. Can the corresponding author please explain? ![file] , 
 More on Corrected Figure 3A and original Figure 3B overlap ![file] , 
 Retracted [4 April 2022] . -------------------------- The Editor in Chief retracted this article because of significant concerns regarding a number of Figures presented in this work, which question the integrity of the data. The Editor-in-Chief therefore no longer has confidence in the integrity of the data in this article. Peng Yang, Ming-zhen Yang, Danlei Chen Si Ying Wang have agreed to this retraction but not to the wording of this retraction notice. Fang Ni, Rui-qing Deng, Guo Qiang, Hua Zhao, Xin-yi Wang, You-zhi Xu, Li Chen, Zhi-jun Chen Li-xin Kan have not responded to any correspondence from the editor publisher about this retraction. ,