Let-7a functions as a tumor suppressor in Ewing's sarcoma cell lines partly by targeting cyclin-dependent kinase 6
Authors: Min Dai
Zhimin Han
Zhongzu Zhang
Shanhu Huang
Lu Huang
Kai Cao
Xiang Chen
Dong Yang
Ping Zhan
Zhiming Yu
Journal: DNA and Cell Biology (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNAs; Ewing's sarcoma; let-7a; tumor progression; cell proliferation
Affiliations: The Department of Orthopedic Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, People's Republic of China., The Department of Child Health Care, Jiangxi Maternal and Child Health Hospital, Nanchang, People's Republic of China.

Abstract:  MicroRNAs play an important role in the development and progression of Ewing's sarcoma (ES). Especially, the expression of let-7a has been reported to be significantly downregulated in various cancers, and can affect the initiation and maintenance of tumor progression. However, the relative effects of let-7a on ES cells and relative mechanisms are largely unknown. In this study, we identified the underexpression of let-7a in human ES cells comparing with the human mesenchymal stem cells. Then, we sought to compensate for its loss through exogenous transfection with let-7a mimic into ES cell lines A673 and SK-ES-1. Restored let-7a expression inhibited cell proliferation, migration, as well as invasion; arrested cell cycle progression; and induced cell apoptosis of both cell lines. Moreover, bioinformatic prediction suggested that cyclin-dependent kinase 6 (CDK6), which is overexpressed and functions as an oncoprotein in ES cells, is a putative target gene of let-7a. Using mRNA and protein expression analysis and luciferase assays, we further identified the target role of CDK6. Finally, we found that restored CDK6 expression in ES cells that had been treated with let-7a mimic before could partly dampen let-7a-mediated tumor suppression. Taken together, our results showed that let-7a acted as a tumor suppressor in ES by targeting CDK6, and it may provide novel diagnostic and therapeutic options for human Ewing sarcoma clinical operation in future. 

Retracted: Yes

PubPeer comments:
 Figure 3A. * Pink boxes: In the A673 panels, the 0h untreated and 0h scramble panels look unexpectedly similar to each other * Blue boxes: In the A673 panels, the 36h untreated and 36h scramble panels appear to show an overlap * Red boxes: In theSK-ES-1 panels, the 24h untreated and 24h scramble panels appear to show an overlap ![file] , 
 Figure 6B C. * Teal boxes: The untreated SK-ES-1 migration panel appears to show an overlap with the si-con SK-ES-1 invasion panel. * Orange boxes: The si-con SK-ES-1 migration panel appears to show an overlap with the untreated SK-ES-1 invasion panel, albeit at a slightly different rotation. ![file] , 
 Retracted [30 March 2022] . -------------------- The Editor-in-Chief of *DNA and Cell Biology* officially retracts the article entitled, u201cLet-7a Functions as a Tumor Suppressor in Ewing s Sarcoma Cell Lines Partly by Targeting Cyclin-dependent Kinase 6,u201d by Zhongzu Zhang, Lu Huang, Zhiming Yu, Xiang Chen, Dong Yang, Ping Zhan, Min Dai, Shanhu Huang, Zhimin Han, and Kai Cao (DNA Cell Biol 33(3):136u2013147; doi: 10.1089 dna.2013.2179) after discovering alerts on the PubPeer platform1 regarding multiple image duplications between Figures 3, 6, and 7. The journal publisher independently confirmed the suspected duplications. The corresponding author of the paper, Dr. Kai Cao, along with all co-authors, were contacted for an explanation but no response was received. DNA and Cell Biology is committed to upholding the rigors of scientific publishing and the veracity of the literature. ,