MiR-101 reduces cell proliferation and invasion and enhances apoptosis in endometrial cancer via regulating PI3K/Akt/mTOR
Authors: Ping Zhu
Min Wang
Qirong Li
Suxia Zhang
Journal: Cancer Biomarkers (2021)
Discipline: CLINICAL MEDICINE
Keywords: PI3K/Akt/mTOR; apoptosis; endometrial cancer; invasion; miR-101

Abstract:  PI3K/Akt/mTOR signaling pathway plays an important role in tumor development. mTOR overexpression and PI3K/ Akt/mTOR signaling pathway enhancement were found in endometrial cancer (EC). MiR-101 was found downregulated in EC. Bioinformatics analysis showed the binding site between miR-101 and the 3'-UTR of mTOR mRNA. This study investigated the role of miR-101 in affecting EC proliferation, apoptosis, and invasion, and mediating mTOR expression. EC tumor tissue and normal endometrial tissue were collected from Jinan maternity and child care hospital. MiR-101 and mTOR expressions were detected. The targeted relationship between miR-101 and mTOR was tested by dual-luciferase reporter gene assay. MiR-101, mTOR, p-mTOR, and p-4EBP1 expressions between HEEC and HEC-1A cells were compared. HEC-1A cells were cultured in vitro and divided into five groups, including miR-NC, miR-101 mimic, si-NC, si-mTOR, and miR-101 + si-mTOR. mTOR, p-mTOR, and p-4EBP1 expressions were compared. Cell apoptosis was evaluated by flow cytometry. Cell malignant proliferation was evaluated by colony formation assay. Cell invasion was determined by Transwell assay. MiR-101 and mTOR expressions significantly declined in EC tissue compared with normal endometrium. MiR-101 showed targeted relationship with mTOR. MiR-101 reduced, while mTOR, p-mTOR, and p-4EBP1 levels elevated in HEC-1 cells compared with HEEC cells. MiR-101 mimic and/or si-mTOR transfection obviously reduced mTOR, p-mTOR, and p-4EBP1 expressions, decreased colony formation, decreased invasion, and enhanced apoptosis in HEC-1A cells. MiR-101 downregulated and mTOR elevated in EC tissue. MiR-101 decreased HEC-1A cell proliferation and invasion, and upregulated apoptosis through targeting mTOR to attenuate PI3K/Akt/ mTOR signaling pathway activity. 

Retracted: No

PubPeer comments:
 *[right]* Figure 4 from [Yu, Guo Wang (2020)] .  Annexin V FITC PI assay results developed via flow cytometry indicating enhanced early and late apoptotic cells. As the lycopsamine concentration increased the number of necrotic and apoptotic cells increased. *[left]* Figure 3 from [Xiao et al (2020)] .  Annexin V PI staining for apoptotic analysis of SCC-1 cancer cells treated with Voacangine. The Figure shows dose-dependent increase in the percentage of apoptotic SCC-1 upon Voacangine treatment . ![file] , 
 *[right]* Figure 7.  Western blotting assay indicating the levels of IL-2 protein after 24h of lycopsamine exposure. *[left]* Figures 4 and 8 from [Hua et al (2020)] .  Effect of indicated concentrations of flavokawainB on the expression of apoptosis-related proteins by western blot analysis ;  Effect at indicated concentrations of flavokawainB on the expression of phosphorylated PI3K AKT signalling pathway proteins . ![file] , 
 The paper has undergone a stealth revision, replacing Figure 4. The version currently provided at the journal website was created modified on 13 January 2021. ![file] The editors may wish to come back and dispose of Fig 7 as well. , 
 #3 I am pleased to report that the editors have indeed uploaded a **third** version of the paper, disposing of Fig 7. This new version was created on 19 January 2021, one day after my critical comment, so I hope everyone is impressed by the speed with which the editors can contact the authors, obtain a less problematic image, and insert it into the PDF. ![file] , 
 Retracted, [July August 2021] .  Following the publication of this article [1], readers drew to our attention that part of the data was unreliable: Figures of this article appeared in other articles (by totally different authors). The authors were requested to provide the raw data and were also asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. Given above, we decided to retract this article. Authors were informed of the retraction. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause. The version now on the website has reverted to the original (apart from the  RETRACTED watermark), rather than the stealth-correction versions shown in Comments #3 and #4. ,