microRNA-758 inhibits the malignant phenotype of osteosarcoma cells by directly targeting and deactivating the Wnt/Œ≤-catenin pathway
Authors: Mengjie Yang
Fengyang Xu
Juwu Chen
Jia Ren
Journal: American journal of cancer research (2019)
Discipline: CLINICAL MEDICINE
Keywords: High mobility group AT-hook 1; Wnt/Œ≤-catenin pathway; malignant phenotype; microRNA-758; osteosarcoma.
Affiliations: Department of Emergency, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan, P. R. China., National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention Beijing 102206, P. R. China.

Abstract:  microRNAs (miRNAs) are frequently aberrantly expressed in osteosarcoma (OS) and are implicated in its development. Dysregulation of miR-758 has been reported in various human malignancies. However, whether miR-758 is involved in the oncogenesis and progression of OS remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction was performed to detect miR-758 expression in OS tissues and cell lines. A series of functional experiments were employed to explore the regulatory effects of miR-758 on the malignant behaviors of OS cells both in vitro and in vivo. The molecular mechanisms underlying the activity of miR-758 in OS cells were also investigated. miR-758 was significantly downregulated in OS tissues and cell lines, and a low miR-758 level was correlated with tumor size, clinical stage, and distant metastasis of patients with OS. OS patients with low miR-758 level exhibited poorer overall survival and worse disease-free survival rates compared to patients with high miR-758 level. In addition, functional assays revealed that miR-758 overexpression led to a significant decrease in OS cell growth and metastasis in vitro, whereas miR-758 inhibition had the opposite effect on OS cells. miR-758 reduced the tumorous growth of OS cells in vivo. Furthermore, high mobility group AT-hook 1 (HMGA1) was identified as a direct target of miR-758 in OS cells. HMGA1 was highly expressed in OS tissues, and its expression was inversely correlated with miR-758 expression. HMGA1 silencing exerted an effect similar to that induced by miR-758 upregulation in OS cells. Restored HMGA1 expression abolished the effects of miR-758 on the malignant phenotypes of OS cells. Moreover, miR-758 regulated the Wnt/Œ≤-catenin pathway in OS cells in vitro and in vivo. To the best of our knowledge, this is the first study to demonstrate that miR-758 may inhibit the aggressive behavior of OS cells in vitro and in vivo by directly targeting HMGA1 and regulating the Wnt/Œ≤-catenin pathway. These results will aid in elucidating the roles of miR-758 and suggest that the miR-758/HMGA1/Wnt/Œ≤-catenin pathway represents a potential therapeutic target in OS. 

Retracted: No

PubPeer comments:
 Figs 2D, 4D, 5D.  Light brown box marks a panel that previously appeared in Figs 2D, 4D, 5D of [Song et al (2018)] .   There may be matches with other panels, or with other papers from this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 Please admire this montage of xenograft tumor images. Green, red, orange, blue boxes mark various pairs that appear to be the same tumors, rotated slightly and viewed from different angles.  Upper row: - Fig 8A from [Dou et al (2020)] . A representative image of tumor xenografts from groups u201csi-FOXD2-AS1u201d and u201csi-NC.u201d Rotated through 90 deg to facilitate comparison. - Fig 8B from [Wang et al (2019)] .  Representative images of tumor xenografts excised from nude mice obtained 4 weeks after subcutaneous injection of Y79 cells transfected with miR-665 mimics or miR-NC. - Fig 7B from [Jiao, Liu Tian (2019)] .  Photograph of tumor xenograft derived from the nude mice injected with miR-493 mimics or miR-NC-transfected Tca8113 cells. Lower row: - **Fig 7A from [Ren et al (2019)] **.  Representative images of the [HOS] tumor xenografts in miR-758 mimics and miR-NC groups. - Fig 6A from [Zhou Li (2019)] .  Photographs of tumor xenografts were obtained from nude mice that were injected with miR-605 mimics or miR-NC transfected H460 cells . Rotated through 90 deg. - Fig 8B from [Yang et al (2019)] .  Photographs of [U251] tumor xenografts from the agomiR-652 and agomiR-NC groups. Rotated through 90 deg. ,