MicroRNA-939-5p directly targets IGF-1R to inhibit the aggressive phenotypes of osteosarcoma through deactivating the PI3K/Akt pathway
Authors: Jian Li
Xiwu Zhao
Dapeng Yu
Journal: International Journal of Molecular Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: microRNA-939-5p; osteosarcoma; tumor-suppressing roles; insulin-like growth factor 1 receptor (IGF-1R); PI3K/Akt pathway
Affiliations: Department of Traumatic Orthopedics, Shandong Provincial Western Hospital, Jinan, Shandong 250022, P.R. China., Department of Orthopedics, Jinan Fourth People's Hospital, Jinan, Shandong 250031, P.R. China., Department of Spine Surgery, Shandong Provincial Western Hospital, Jinan, Shandong 250022, P.R. China.

Abstract:  The dysregulation of microRNA‚Ä?39‚Ä?p (miR‚Ä?39) is involved in the development of multiple types of human cancer. However, the expression and roles of miR‚Ä?39 in osteosarcoma (OS) have yet to be clarified. The expression level of miR‚Ä?39 in OS was measured using reverse transcription quantitative polymerase chain reaction (RT‚ÄëqPCR). A Cell Counting Kit‚Ä? assay, flow cytometry analysis, Transwell migration and invasion assays, and a tumor xenograft assay were employed to explore the effects of miR‚Ä?39 in OS cells. Bioinformatics analysis, RT‚ÄëqPCR, western blot analysis and luciferase reporter assays were performed to explore its underlying mechanism. Expression of miR‚Ä?39 was decreased in both OS tissues and cell lines. The decreased miR‚Ä?39 expression was notably correlated with clinical stage and distant metastasis in patients with OS, where low miR‚Ä?39 levels were correlated with lower overall survival. miR‚Ä?39 overexpression decreased OS cell proliferation, migration and invasion in vitro; induced cell apoptosis, and impaired tumor growth in vivo. Mechanistically, insulin‚Äëlike growth factor 1 receptor (IGF‚Ä?R) was characterized as direct target gene of miR‚Ä?39 in OS. The tumor‚Äësuppressing effects of miR‚Ä?39 in OS cells were imitated by IGF‚Ä?R knockdown. In addition, exogenous IGF‚Ä?R expression abolished the tumor suppressive roles of miR‚Ä?39 in OS cells. miR‚Ä?39 was implicated in the deactivation of the PI3K/Akt pathway in OS in vitro and in vivo through regulating IGF‚Ä?R expression. The present study demonstrated that miR‚Ä?39 exerted tumor‚Äësuppressing roles in the malignancy of OS cells by directly targeting IGF‚Ä?R and inactivating the PI3K/AKT pathway. Therefore, this miRNA may be a promising target for anticancer therapy in patients with OS. 

Retracted: No

PubPeer comments:
 Figs 2C, 4D, 5E.  The carmine box marks a panel that also appeared in Figs 1F, 4B, 4G of [Zhang, Long Hu (2020)] :   There may be other matches with other panels, or with other papers in this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit#gid=0 , 
 Figs 2D E, 4E F, 5F G.  Figs 2D E, 5D E, 6D E from [Jaio, Liu Tian (2019)] . I have replaced one panel with the author s correction from a comment in that thread.  Blue rectangles mark the same panel appearing in both papers. How to explain the duplication? , 
 *[left]* Fig 7A.  The images of [HOS] tumor xenografts obtained from miR-939 and miR-NC groups . *[right]* Fig 7A from [Zhao et al (2018)] .  Images of [TPC-1] tumor xenografts from the miR-766 mimics and miR-NC groups at 30 days .  Two tumors seem to have been used in both photoshoots. , 
 - *[above]* Fig 2D E. - *[below]* Fig 2D E from  MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1 ([Cheng et al 2020] ) **[retracted]**.  , 
 - *[left]* Fig 5D from  Long Noncoding RNA ST7-AS1 Upregulates TRPM7 Expression by Sponging microRNA-543 to Promote Cervical Cancer Progression ([Qi et al 2020] ). - *[right]* Fig 4F.  , 
 Retracted [18 August 2022] .  Following the publication of the above paper, it was drawn to the Editors attention by a concerned reader that certain of the flow cytometric data featured in Figs. 2C, 4D and 5E, the Transwell cell migration and invasion assay data shown in Figs. 2D and E, 4E and F, and 5F and G, and the tumor images shown in Fig. 7A, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. ,