<p>MicroRNA-761 targets FGFR1 to suppress the malignancy of osteosarcoma by deactivating PI3K/Akt pathway</p>
Authors: Zhongzhe Lv
Jianchuan Wang
Jianmin Lu
Jinming Ma
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/Akt pathway; fibroblast growth factor receptor 1; microRNA-761; osteosarcoma; pathogenesis.
Affiliations: Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Liaoning 116001, People's Republic of China., School of Graduate Studies, Zunyi Medical University, Guizhou 563000, People's Republic of China.

Abstract:  Purpose: MicroRNA-761 (miR-761) has been reported to be deregulated in many types of human cancers and play important roles in cancer genesis and progression. However, the biological roles of miR-761 in osteosarcoma (OS) and the underlying mechanisms remain largely unknown. Methods: The expression of miR-761 in OS tissues and cell lines was analyzed using RT-qPCR. A series of gain-of-function tests were performed, and status of malignancy was evaluated on basis of proliferation, migration, invasion, and apoptosis using different assays to determine the regulatory roles of miR-761 in OS cells in vivo and in vitro. Notably, the mechanisms underlying the action of miR-761 in the pathogenesis of OS were investigated using bioinformatic analysis, luciferase reporter assay, RT-qPCR and Western blotting. Results: The results showed that miR-761 expression was decreased in OS tissues and cell lines and is closely correlated with clinical stage and distant metastasis in OS patients. Patients with OS having low miR-761 expression showed worse prognosis compared to OS patients with high miR-761 expression. Restoring the miR-761 expression level decreased OS cell proliferation, migration, and invasion in vitro; promoted cell apoptosis in vitro; and impaired tumor growth in vivo. In addition, fibroblast growth factor receptor 1 (FGFR1) was found as a direct target gene of miR-761 in OS cells. Furthermore, silencing FGFR1 expression stimulated the tumor-suppressing roles of miR-761 upregulation in OS cells, whereas the activity of miR-761 overexpression in OS cells was abolished by the restoration of FGFR1 expression. Moreover, restoration of miR-761 expression deactivated the PI3K/Akt pathway in vitro and in vivo. Conclusion: These results suggest that miR-761 plays anti-cancer roles in OS by directly targeting FGFR1 and deactivating the PI3K/Akt pathway. The newly identified miR-761/FGFR1/PI3K/Akt pathway partially illustrates the mechanism of OS pathogenesis and presents a novel candidate therapeutic target for antitumor therapy. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4C, 5C. ![file] One panel also features in Figs 2D, 4D, 5D of [Chen et al (2019)] . ![file] Here in context: ![file] There may be other panels shared, with this or with other papers from the same *oeuvre*. Like a trout in a milk-bottle, a single match is enough to call out for an explanation. , 
 Clockwise from left: - Fig 7A from [Wang et al (2018)] .  The representative images of the miR-769 mimics and miR-NC [SW480] tumor xenografts. Rotated through 90 deg to facilitate comparison. - Fig 7B from [Song et al (2018)] .  Representative images of the miR-532 mimics and miR-NC [SW480] xenograft tumors . - **Fig 7A from [Lv et al (2019)] **.  The representative images of [HOS] tumor xenografts obtained from agomir-NC and agomir-761 groups . - Fig 7A from [Lyu et al (2019)] .  Representative images of the [Y79] tumor xenografts derived from miR-485 mimics or miR-NC groups . - Fig 7A from [Yao et al (2018)] .  Photographs of tumor xenografts derived from miR-641 mimics- or miR-NC-transfected HeLa cells . ![file] Certain pairs of tumors appear to be the same (colored boxes). All five institutions seem to be using the same distinctively-battered ruler. , 
 Figs 2C, 4C, 5C again. ![] . Light brown box added, to mark a panel that shares many points with a panel from Figures of [Ye et al (2020)] . ![] In context: ![] , 
 Fig 2C again: ![] One panel shares most of its points with Figs 2C, 5B of [Wang et al (2020)] . ![] ![] , 
 Retracted [28 September 2021] . --------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2C, 5C and 7A with similar images from unrelated articles, specifically: - Figure 2C, panel HOS agomir-761 appears to have been duplicated with a similar image in Figure 5B from Wang et al, 2020 . - Figure 5C, panel HOS agomir-NC appears to have been duplicated with a similar image in Figure 5D from Chen et al, 2019 . - Figure 5C, panel U2OS agomir-761+pCMV-FGFR1 appears to have been duplicated with a similar imges in Figure 2E from Ye et al, 2020 . - Figure 7A, appears to have been duplicated with similar images in Figure 7B from Song et al, 2018 (http: www.ajcr.us files ajcr0088433.pdf). The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. 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. ,