LINC00449 regulates the proliferation and invasion of acute monocytic leukemia and predicts favorable prognosis
Authors: Zhuojun Zheng
Yuan Shi
Xiao Zheng
Yuandong Zhu
Journal: Journal of Cellular Physiology (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AML; FOXD3; LINC00449; invasion; miR-150.
Affiliations: Laboratory of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China., Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China., Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China., Cancer Immunotherapy Engineering Research Center of Jiangsu Province, Changzhou, Jiangsu, China., Institute of Cell Therapy, Soochow University, Soochow, Jiangsu, China.

Abstract:  Acute myeloid leukemia (AML) is a highly aggressive disease that causes high mortality. Long noncoding RNA (lncRNA) have studied in recent years that could be a potential biomarker and therapeutic target. Therefore, it is urgently necessary to explore the novel lncRNAs in AML. Microarray analysis was performed to determine the differentially expressed lncRNAs between mononuclear cells of AML and normal samples. The biological function of lncRNA on cell proliferation and migration was measured in vitro. The predicted downstream target of lncRNA was validated by dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments. The tumor formation and metastasis study were conducted in vivo. The expression of lncRNA in clinical samples was determined by a quantitative reverse transcription-polymerase chain reaction. LINC00449 was one of the most differentially expressed lncRNA which is mainly located in the cytoplasm. We found that overexpression of LINC00449 could inhibit the cell proliferation and invasion of AML cells in vitro and in vivo. Besides, miR-150 was identified as the downstream target gene that was negatively regulated by LINC00449 and FOXD3 was targeted by miR-150. The results were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, rescue experiments, and in vivo assays. Patients with AML with high expression of LINC0049 may characterize a favorable survival. All the above-mentioned findings indicated that the LINC00449/miR-150/FOXD3 signaling pathway might represent a novel prognostic biomarker or therapeutic target for the treatment of AML. 

Retracted: No

PubPeer comments:
 figure 4f ![file] , 
 There is a recent extensive correction for this paper. They have changed all the tumors in Figure 6c. I am wondering why? Interestingly, in the corrected Figure 4f, they have provided a new manipulation in the corrected figure... The Figure numbers in the Erratum are wrong. ![file] , 
 If not the previous issues are not enough for a retraction, I can continue: Two of the micrographs in this falsified article are reused from an earlier publication in Scientific Reports: ![file] , 
 #3 Comment #1 missed an overlap between the NC panel of 4f and the two duplicated panels. ![file] In the revised version the panels have been shaved along the edge to remove the overlap, but this does not change the fact that  NC and  miR-150-mimic are contiguous details from a single image. , 
 #3 *Two of the micrographs in this falsified article are reused from an earlier publication in Scientific Reports* **Three** micrographs. ![file] , 
 #2 At least one of the tumors was either manipulated in the original version, or manipulated in the replacement (or both). Are the editors comfortable with this? ![file] The (modified) reappearance of a tumor also implies that one or other array was composed digitally rather than on a bench top (or both were). ![file] , 
 #5 **Six** micrographs when one adds Fig 2F from the SciRep paper ([Yang et al 2019] ) to the mix. ![file] , 
 Thank you for comments. This article needs to be retracted as big problems presented. I will check the data and contact the editors. , 
 #8 Bravo for your honesty, loyalty and brave decision! , 
 If the above is not enough, please see the falsification of Figure 6A, where all the tumors are taken from an earlier publication (Zhou F et al., Onco Targets Ther 2019). I am not sure if I will call it honesty, loyalty and a brave decision to first falsify a publication, and then correcting it by introducing even more falsifications. ![file] , 
 #6 Further comparisons of the original Fig 6C and the replacement correction. Perhaps I am imagining the points of similarity between certain tumors and their replacements, but to my mind, they are what I would expect if the originals had been smeared, stretched, stirred around and airbrushed within digital software. ![file] The rulers providing scale in the arrays have identical scrapes and scratches, but numbers decreased by 10. ![file] , 
 Retracted [16 March 2022] . ----------------------- The above article, published online on 21 January 2020 in Wiley Online Library , and the corresponding Erratum, published on July 30 2020 , have been retracted by agreement between, the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed after the authors asked to correct their article, and following an investigation based on allegations raised by a third party. The authors admit substantial mistakes during figure compilation for this manuscript. Additionally, some image elements of the experimental data were published elsewhere in a different scientific context. The authors provided additional experimental results. However, the experiments in the published article are considered unreliable and do not sufficiently support the conclusions. The authors disagree with this decision. ,