MicroRNA-154 functions as a tumor suppressor in osteosarcoma by targeting Wnt5a
Authors: Chunyan Meng
Dongxu Zhao
Minglei Zhang
Hui Zhou
Wei Zheng
Hongping Yuan
Journal: Oncology Reports (2016)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miRNA-154; osteosarcoma; tumorigenesis; gene expression
Affiliations: China‑Japan Union Hospital of Jilin University, Nanguan, Changchun 13033, P.R. China., The Fourth Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract:  MicroRNAs (miRNAs) are small non-coding RNAs that are involved in tumor initiation and development by suppressing target gene expression. miRNA-154 has been shown to be important in tumorigenesis in many types of cancers. However, its role in osteosarcoma (OS) remains unknown. In the present study, we focused on the roles and mechanisms of miR‑154 in OS development. The results of quantitative RT‑PCR showed that miR‑154 expression was decreased in primary OS tumor samples and cell lines compared to levels in the matched adjacent normal tissues and human normal osteoblast cells (NHOst). Restoration of expression in U2OS cells inhibited cell proliferation, colony formation, migration and invasion, as well as induced cell cycle arrest at the G1 stage. Bioinformatic prediction suggested that Wnt5a is a target gene of miR‑154. It was further verified that Wnt5a is a target gene of miR‑150 in OS cells using luciferase assay, mRNA and protein expression analysis. Wnt5a was upregulated in OS cell lines and primary tumor samples, and its mRNA expression level was negatively correlated with the miR‑154 level in the OS tissues. Restored expression of Wnt5a weakened miR‑154‑mediated suppression of tumor progression. Taken together, these findings suggest that miR‑154 functions as a tumor suppressor in OS by partially suppressing Wnt5a expression. 

Retracted: Yes

PubPeer comments:
 The microscopy images are rather surprising. In particular, the absence of any background in the fluorescence image gives the impression that those oval shapes (supposed to be cells) have been copied and pasted. Furthermore, the bottom right and bottom left are identical. The top and bottom centre are identical too, except a 90 degrees rotation. ![file] , 
 #1 Dear Dr. Raphau00ebl Lu00e9vy, I am Weijie Shi, the first author of the article. Thank you for your valuable comments. Sorry for my late response due to the mailbox setting reasons. We carefully checked the manuscript immediately upon seeing your comments and found that there seemed to be some errors in Figure 6. Due to the limitations of our laboratory s working conditions and our weakness in biological experiments, the cellular imaging experiment of Figure 6 was completed by the collaborator in other institutions. The experimental results at that time showed that the prepared graphene quantum dots (GQDs) were indeed capable of cellular imaging, which was true and reliable. However, due to the lower performance of fluorescence microscope at that time, we selected the cell imaging area and adjusted the picture contrast in order to present a clear effect, which might result in the errors of the Figure 6 due to the confusion of the similar cell appearance. Regrettably, due to the lack of experience in cell experiments, we didnu2019t find the problems of Figure 6. We sincerely apologize for the mistakes. We have tried to find the raw data, but unfortunately, the raw data of Figure 6 is unable to be found because of the long time, the personnel changes in institutions and the replacement of equipments. We are very sorry for that. In order to further evaluate the reliability of our conclusions, we carried out the repeated experiments of cellular imaging by a high-resolution laser confocal microscope (LSM880 with Airyscan, Zeiss, Germany), and the results were shown in Figure R6. Compared to the bright field image in Figure R6a, the bright ufb02uorescence of GQDs inside the cells can be obviously observed (Figure R6b), which showed that the GQDs can be used for cell imaging. The results are consistent with the scientific conclusions of our manuscript. We will immediately contact the editorial office to make the necessary corrections. We sincerely apologize for any inconvenience caused by our negligence to the readers. Thanks again for your comments. ![file] Figure R6 Confocal fluorescence images of chicken embryo cells after incubation with GQDs (0.2 mg.mL-1): (a) bright field image, (b) fluorescence image under 405 nm laser excitation. Kind regards Weijie Shi ,