MicroRNA-124 suppresses the migration and invasion of osteosarcoma cells via targeting ROR2-mediated non-canonical Wnt signaling
Authors: Yihe Hu
Jun Wan
Can Zhang
Hongbo He
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; tumorigenesis; miR-124; osteosarcoma; cell migration

Abstract:  MicroRNAs (miRs) have been implicated in tumorigenesis through inhibition of the expression of their target genes at post-transcriptional levels. miR-124 has been found to be downregulated in many malignant tumors including osteosarcoma (OS). However, the detailed mechanism of miR-124 in the regulation of OS malignant phenotypes remains largely unclear. Here we aimed to explore the role of miR-124 in mediating OS cell migration and invasion, as well as the underlying regulatory mechanisms. Real-time RT-PCR data showed that miR-124 was frequently downregulated in OS cell lines compared to normal human osteoblast cells. We further conducted bioinformatic analysis and a luciferase reporter assay, and identified receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a novel target of miR-124. Furthermore, we found that ROR2 was significantly upregulated in OS cell lines compared to normal human osteoblast cells, and miR-124 negatively mediated the protein level of ROR2 in U-2OS and Saos-2 cells. Moreover, transfection with miR-124 mimics significantly suppressed migration and invasion in the U-2OS and Saos-2 cells, while overexpression of ROR2 in the miR-124-transfected OS cells reversed the inhibitory effect of miR-124 upregulation on OS cell migration and invasion. In addition, we found that overexpression of miR-124 significantly suppressed the activity of non-canonical Wnt signaling, downstream of ROR2. Based on these findings, we suggest that miR-124 may inhibit OS metastasis, partly at least, via targeting ROR2 and thus suppressing the activity of ROR2-mediated non-canonical Wnt signaling. 

Retracted: Yes

PubPeer comments:
 Fiig 2C,  Transwell assays were performed to determine the cell migratory and invasive capacities in each group. Control, Saos-2 and U-2OS cells without any transfection , and 5B,  Transwell (B) assays were performed to determine the cell ... invasive capacities of the Saos-2 and U-2OS cells transfected with miR-124 mimics, or co-transfected with miR-124 mimics and the ROR2 plasmid . ![file] Colored rectangles mark similar panels in Figs 2(C) and 4(C) of [Jiao et al (2016)] . ![file] Also *[above]* Fig 4C from [Lai, Chen Li (2015)] .  a Transwell assay were performed to examine the cell proliferation of AGS cells transfected with miR-133a mimics, miR-133a inhibitor, or co-transfected with miR-133a mimics and FSCN1 plasmid. Control: AGS cells without any transfection. *[below]* Figs 3(B), 6(B) from [Shi et al (2015)] .  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with NC scramble miRNA or miR-204 mimics, respectively. Control, Saos-2 and U-2 OS cells without any transfection ...  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with Sirt1 siRNA or co-transfected with miR-204 mimics and the Sirt1 plasmid, respectively. Control, Saos-2 and U-2 OS cells without any transfection . ![file] , 
 Fig 2B.  Wound-healing ... assays were performed to determine the [**U-2 OS and Saos-2**] cell migratory ... capacities in each group . ![file] Color coded to show panels shared with Figs 3A, B and 8A,B  [**NSCLC**] Wound healing assay from [Liu et al (2017)] . ![file] , 
 Thank you for the concerns about our paper. We have carefully reviewed the data and acknowledge that there are some misuses of the images in the mentioned figures. To resolve these, we are re-performing the experiments and will send a request to the journal for Erratum with the correct figures. Thank you again. , 
 Thank you for the concerns about our paper. We have carefully reviewed the data and acknowledge that there are some misuses of the images in the mentioned figures. To resolve these, we are re-performing the experiments and will send a request to the journal for Erratum with the correct figures. Thank you again. , 
 Thank you for the concerns about our paper. We have carefully reviewed the data and acknowledge that there are some misuses of the images in the mentioned figures. To resolve these, we are re-performing the experiments and will send a request to the journal for Erratum with the correct figures. Thank you again. , 
 Retracted [7 June 2021] . -------------------------------------------- Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 2C and 5B) were strikingly similar to data appearing in different form in other articles by different authors, which were either already under consideration for publication or had already been published elsewhere at the time of the present article s submission. Owing to the fact that the contentious data in the above article were either already under consideration for publication, or had already been published elsewhere, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,