MicroRNA-200b acts as a tumor suppressor in osteosarcoma via targeting ZEB1
Authors: Zhenhan Deng
Min Tu
Wenfeng Xiao
Yuling Hu
Chao Zeng
Yusheng Li
Wei Jiang
Zixun Dai
Journal: OncoTargets and Therapy (2016)
Discipline: CLINICAL MEDICINE
Keywords: invasion; metastasis; microRNA-200b; migration; osteosarcoma
Affiliations: Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, People's Republic of China., Department of Orthopedics, Second People's Hospital of Jingmen, Jingmen, Hubei, People's Republic of China., Department of Bone and Joint, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, People's Republic of China., Department of Orthopedics, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China., Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.

Abstract:  Osteosarcoma is the most common type of cancer that develops in bone, mainly arising from the metaphysis of the long bones. MicroRNA (miR)-200b has been found to generally act as a tumor suppressor in multiple types of human cancers. However, the detailed role of miR-200b in osteosarcoma still remains to be fully understood. This study aimed to investigate the exact role of miR-200b in the progression of osteosarcoma and the underlying mechanism. Real-time reverse transcription-polymerase chain reaction data showed that miR-200b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Low miR-200b level was associated with the advanced clinical stage and positive distant metastasis. Besides, it was also downregulated in osteosarcoma cell lines (U2OS, Saos2, HOS, and MG63) compared to normal osteoblast cell line NHOst. In vitro study showed that restoration of miR-200b led to a significant decrease in proliferation, migration, and invasion of osteosarcoma cells. Moreover, ZEB1 was identified as a target gene of miR-200b, and its expression levels were negatively mediated by miR-200b in osteosarcoma cells. In addition, ZEB1 was significantly upregulated in osteosarcoma cells compared to the normal osteoblast cell line NHOst, and inhibition of ZEB1 expression also suppressed the proliferation, migration, and invasion in osteosarcoma cells. Finally, we showed that ZEB1 was frequently upregulated in osteosarcoma tissues compared to their matched adjacent normal tissues, and its expression was reversely correlated to the miR-200b levels in osteosarcoma tissues. Based on these findings, our study suggests that miR-200b inhibits the proliferation, migration, and invasion of osteosarcoma cells, probably via the inhibition of ZEB1 expression. Therefore, miR-200b/ZEB1 may become a potential target for the treatment of osteosarcoma. 

Retracted: Yes

PubPeer comments:
 Figs 3B, 7B. Transwell assays.  I set up a spreadsheet to include the various papers using this versatile suite of Transwell images to represent all possible combinations of cell-lines and treatments. This is the 35th manifestation. For comparison: Fig 3 C D from [Zhang et al (2016)] .  Transwell assay were performed to examine the migratory and invasive capacities of Saos-2 and U2OS cells transfected with miR-205 mimic or miR-negative control (NC) mimic , and Fig 7C D,  Transwell assay were performed to examine cell migration and invasion of MG63 or U2OS cells transfected with miR-205 mimic, or co-transfected with miR-205 mimic and RUNX2 plasmid .  Figs 4D, 6D from [Xia et al (2016)] .  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 .  , 
 Retracted [24 August 2021] . ---------------------------------------- The Editor and Publisher of *OncoTargets and Therapy* wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figures 3B and 7B which appear to have been duplicated with similar images from other unrelated articles. The authors responded to our queries but were unable to provide an explanation for the alleged image duplication and were unable to verify their original data. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,