MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1
Authors: Yixue Gu
Chengkun Wang
Guopei Zheng
Zhijie Zhang
Ying Song
Min Deng
Zhimin He
Ye Cheng
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: miRNAs; progression; metastasis; cancer; roles
Affiliations: Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR China; Medical School, University of South China, Hengyang, Hunan, PR China., Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, PR China.

Abstract:  miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer. 

Retracted: Yes

PubPeer comments:
null, 
 2019 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0227503 After publication of this article [1], concerns were raised that there appear to be regions of overlap between the following panels of Figs 3, 5, and 6: Fig 3B, 95D and 95D con panels Fig 3B, 95D miR-493 panel and Fig 5E, H1975 si-E2F1 panel Fig 5D, 95D si-E2F1, 95D miR-493+E2F1, and Fig 5E, H1975 miR-493+E2F1 ERK data in Fig 6A lanes 1, 2, and Fig 6C lanes 3, 4 ERK data in Fig 6A, lanes 2, 3, 4 and Fig 6B, lanes 1, 2, 3 In addition, there appear to be vertical discontinuities in the following western blot panels: Fig 4E, E2F1 blot, after lane 3 Fig 6A, p-ERK blot, before lane 3 Fig 6B, p-Akt blot, before lane 2 Fig 6B, p-ERK blot, before lane 3 Fig 6B, p-GSK3u03b2 blot, before lane 5 Fig 6C, p-Akt blot, before lane 3 Fig 6C, p-ERK blot, after lane 1 The underlying data for the study were not included with the article, although the Data Availability statement notes, u201cAll relevant data are within the paper and its Supporting Information files.u201d The authors noted that duplications in Figs 3B, 5D, and 5E resulted from figure preparation errors, and that data from the Fig 3 experiments were errantly reported in Fig 5. They provided replacement data for Figs 5D and 5E, along with several original images for Fig 3; quantitative data for Fig 3A data were not provided. Notably, 7 out of 10 images provided for the H1975 miR-493 experiment in Fig 3B indicated results similar to the H1975 control data, calling into question whether the corresponding figure panel was truly representative of this experimentu2019s results. The underlying data for Fig 4E are not available. The original image data provided in support of Fig 6 indicated that for some panels the labels on the figure did not align with labels on the raw image data, and or image data had been spliced to rearrange lanes. In addition, according to the raw image data provided, the wrong ERK data were reported in all three panels and different u03b2-actin controls applied to different experiments shown in each figure panel. The data in the figure did not appear to match the raw data provided for Fig 6B p-GSK3u03b2 lanes 5, 6 (H1229 data), Fig 6C p-Akt, or Fig 6C p-ERK lane 1. Original data are no longer available to support Fig 6A GSK3u03b2; Fig 6B ERK, E2F1, Akt, p-Akt; and Fig 6C ERK, u03b2-actin. In discussing these issues, the authors commented that in general western blot experiments included internal reference protein controls (e.g., u03b2-actin), but for technical reasons they obtained target protein and control data using different blots in some cases. Similarly, they noted that in some cases p-ERK and ERK data were obtained using different blots. This aspect of the experimental design calls into question the validity of the control data for the phosphorylation experiments; without sufficient controls the western blot experiments do not adequately support the reported results and conclusions about effects of miR-493 on the Akt and ERK pathways. Underlying data for most other results reported in the article are available from the authors. The data indicated that G1 and G2 percentages are misreported in Fig 2C for H1975 miR-493, they ought to be reported as 68.05% and 8.0%, respectively. In addition to the image concerns, there is text overlap between this article [1] and previously published articles. Specifically, there is overlap with [2] including but not limited to: in the Introduction, u201cbeen expanded to include a type of non-protein-coding RNA [u2026] crucial roles in tumorigenesisu201d the majority of the text in the Results subsection titled, u201cE2F1 regulations ERK and PI3K-AKT pathway in 95D and H1975 cellsu201d the discussion of the AKT and ERK pathways in the third paragraph of the Discussion There is also text overlap with [3] in the second paragraph of the Discussion: u201cis tightly regulated [u2026] aberrant growth of neoplastic cells.u201d In light of the number of data reporting concerns, the unavailability of data for several figures of concern, the unresolved issues involving Figs 4 and 6, and the text overlap, which call into question the overall reliability of the reported results and conclusions, the PLOS ONE Editors retract this article. The authors apologize for the issues with this article and report that they are conducting additional experiments to examine the reliability of the results in question. YG and ZH agreed with the retraction. YC, YS, ZZ, MD, CW, and GZ did not reply or could not be reached. References 1.Gu Y, Cheng Y, Song Y, Zhang Z, Deng M, Wang C, et al. (2014) MicroRNA-493 Suppresses Tumor Growth, Invasion and Metastasis of Lung Cancer by Regulating E2F1. PLoS ONE 9(8): e102602. https: doi.org 10.1371 journal.pone.0102602 pmid:25105419 2.Deng M, Tang H, Zhou Y, Zhou M, Xiong W, Zheng Y et al. (2011) miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma. J. Cell Science 124: 2997u20133005. https: jcs.biologists.org content 124 17 2997.long? pmid:21878506 3.Alla V, Engelmann D, Niemetz A, Pahnke J, Schmidt A, Kunz M, et al. (2010) E2F1 in Melanoma Progression and Metastasis. Journal of the National Cancer Institute 102(2): 127u2013133. https: doi.org 10.1093 jnci djp458 pmid:20026813 , 
 Reposting here the concerns about Figure 6, since that image was eaten during the PubPeer upgrade. ![file] , 
 As a post-mortem, Image Twin found some more overlaps in Figure 5. Here is a redo. ![file] ,