MicroRNA-145 inhibits the activation of the mTOR signaling pathway to suppress the proliferation and invasion of invasive pituitary adenoma cells by targeting AKT3 in vivo and in vitro
Authors: Peng-Fei Wu
Yan-Dong Fan
Ting-Rong Zhang
Serick Duysenbi
Kai Zhou
Guo-Jia Du
Zhao-Hai Feng
Journal: OncoTargets and Therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: AKT3; invasion; invasive pituitary adenoma; mTOR signaling pathway; microRNA-145
Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.

Abstract:  Purpose: This study was designed to explore how miR-145 regulates the mTOR signaling pathway in invasive pituitary adenoma (IPA) by targeting AKT3. Methods: A total of 71 cases of IPA tissues and 66 cases of non-IPA tissues were obtained in this study. In vitro, the IPA cells were assigned into blank control, empty plasmid, miR-145 mimic, miR-145 inhibitor, miR-145 mimic + rapamycin, miR-145 inhibitor + rapamycin and rapamycin groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect the protein expressions of PI3K, AKT3, mTOR mRNA and the mRNA expression of miR-145 both in vivo and in vitro. Additionally, the S6K and RPS6 mRNA and protein expressions as well as the relative phosphorylation levels were determined in vitro. MTT assay, flow cytometry and transwell assay were used to testify the cell proliferation, apoptosis and invasion ability, respectively. Results: The IPA tissues exhibited significantly lower expression of miR-145 but higher PI3K, AKT3 and mTOR mRNA and protein expressions when compared with the non-IPA tissues. Compared with the blank control and empty plasmid groups, the miR-145 mimic group showed significantly decreased PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as phosphorylation levels; besides, the IPA cell proliferation, migration and invasion ability were strongly inhibited, accompanied with the increased number of apoptotic cells. In the miR-145 inhibitor group, the PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as the phosphorylation levels were significantly increased; cell proliferation, migration and invasion ability were remarkably elevated, accompanied with reduced apoptotic cell number. Conclusion: The study demonstrates that miR-145 inhibits the mTOR signaling pathway to suppress the IPA cell proliferation and invasion and promotes its apoptosis by targeting AKT3. 

Retracted: Yes

PubPeer comments:
 Figure 6: Flow cytometry Panels C, F and G have unexpected similarities despite representing different experimental groups. ![file] , 
 Figure 7: Cell Panels B and F share majority but not all the cells in the picture despite representing different experimental groups. ![file] , 
 Figure 8: Apparent duplication - Panels B and F ![file] , 
 Figures 7 and 8 also appear to have duplications with other papers: Figure 7 and 8 of this paper: ![file] ![file] Figure 6 and 12 of [Li 2015](http: pubpeer.com publications B3DE3BD6ED69BF2D2D0EAA458B757F): ![file] ![file] Figure 5 of[ Ba 2017](http: pubpeer.com publications AEFB35F8F72B292D427FFDD6F360D9): ![file] Figure 8 of [Qiao](http: pubpeer.com publications A2B9F909208655184858F1F3293580): ![file] Figure 5 of [Zhang 2019](http: pubpeer.com publications C0FB404E2743150737C4CDD2A8CF17): ![file] , 
 [Retracted 14 July 2020] :  The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. We were notified of potential image manipulation in the published article. The issues relate to the alleged duplication of Panels C and G in Figure 6, Panels B and F in Figure 7 and Panels B and F in Figure 8. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication or provide satisfactory raw data relating to the figures in question. The editor determined the findings of the study were no longer valid and requested for the article to be retracted. With the retraction on the record, I figure that it is safe to speculate about a possible papermill provenance for this paper. Specifically, the  contractor papermill [discussed in blogposts] and itemised in [a Google document] . One could also speculate about when the publishers responsible for the other papers using the same images (some of them listed in #4) will follow the lead of Dove Press. ,