Effects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K/AKT/mTOR signal pathway
Authors: X-J Zhao
W-H Tan
Y-X Jin
D-D Dong
Q Liu
W Liu
F Wang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PI3K/AKT/mTOR pathway; cervical cancer; miR-214; mTOR expression; cell proliferation
Affiliations: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. .

Abstract:  Objective: PI3K/AKT/mTOR pathway plays important roles in tumor pathogenesis. mTOR is up-regulated and miR-214 is down-regulated in cervical can-*cers. This study investigated whether miR-214 regulated mTOR expression and affected cervical cancer cell proliferation, apoptosis or invasion. Patients and methods: Cervical cancer tissues were collected in parallel with normal epithelium for measuring the expression of miR-214 and mTOR. Dual luciferase expression assay was performed to evaluate the targeted relationship between miR-214 and mTOR. In vitro cultured SiHa cells were treated with miR-214 mimic or si-mTOR followed by measuring mTOR, p-mTOR and Bcl-2 expression. Cell apoptosis, proliferation and invasion were measured by flow cytometry and transwell assay. Results: Bioinformatics analysis showed targeted binding sites between miR-214 and 3'-UTR of mTOR mRNA. Dual luciferase reporter assay confirmed this regulatory relationship between miR-214 and mTOR mRNA. Compared to normal cervical epithelium, cancer tissues had lower expression of miR-214 and higher mTOR, both of which were correlated with TNM stage and tissue pathology grade. Compared to Ect1/E6E7 cells, SiHa cells had lower level of miR-214 and higher mTOR/p-mTOR and Bcl-2 expression. Transfection of miR-214 mimic or si-mTOR significantly decreased mTOR/p-mTOR or Bcl-2 expression, inhibited cell proliferation or invasion, and enhanced cell apoptosis. Conclusions: miR-214 down-regulation plays a role in elevating mTOR expression and in facilitating cervical cancer pathogenesis. Over-expression of miR-214 inhibits cervical cancer cell proliferation or invasion, and facilitates apoptosis via targeted inhibition of mTOR expression. 

Retracted: Yes

PubPeer comments:
 At left:  Figure 4. Inhibition of miR-155 expression attenuated RCC cell proliferation and invasion, and promoted cell apoptosis. ... D, Flow cytometry detection of cell apoptosis.  From [Wei et al (2017)] . At right:  Figure 4. MiR-214 overexpression weakened proliferation or invasion potency of CC cancer cells and facilitated their apoptosis.... D, Flow cytometry for cell apoptosis.  ![file] The panels are slightly customised with additional stippling in the two upper quadrants but are 99% identical, despite the different miR and carcinoma cell-line, and the lack of overlap in authors between the two papers. , 
 #1 Also notable in these two papers (and others) are the Western Blots. Here following a sharp-edged convention, like blobs of black paint on chrome. ![file] , 
 There is no obvious connection between the e-address provided for correspondence (shuliyang8686@163.com) and the name of the corresponding author. , 
 Some time in the last week or so, the journal wished the paper into the cornfield: https: www.europeanreview.org article 22242 Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cEffects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K AKT mTOR signal pathway, by F. Wang, W.-H. Tan, W. Liu, Y.-X. Jin, D.-D. Dong, X.-J. Zhao, Q. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 1891-1898u2013DOI: 10.26355 eurrev_201804_14711u2013PMID: 29687840u201d has been withdrawn. The Publisher apologizes for any inconvenience this may cause. , 
 #4 We sincerely apologize for the mistakes in our study and the related trouble caused to you. The first email you sent me in 2020 03 11 was blocked by email software, so that I found it in junk mail box till June. We have sent you the original raw data in 2020 07 09 (v.doria@verduci.it). Then to confirm the scientificity of the study, we repeated experiments about the confused results, including western blot, transwell and cell cytometry. As expected, the results were consistent with those in the article, and the raw data of repeated results was also sent to you (v.doria@verduci.it) in 2020 07 19. The prove pictures of the sending email are provided below. We will also send all the raw data to the official email of the Journal (eurrevmed@publishingmanager.org, europeanreview@verduci.it) later. At last, we sincerely ask for an oppotunity to correct the confused results (figure 2B, 3B, 4A and 4D) and avoid withdrawing of the study. #3 The email address is registered by corresponding author Liu Qin several years ago. We will stop using the emial-address for submitting in future to prevent the similar problem. #2 We are really sorry for the mistake. We have repeated all the western blot experiments in this study, and got consistent results with that in this artile. The raw data had been provided and sent to the Journal (v.doria@verduci.it). #1 We are sorry for the confused mistake. We entrusted a biological company for the cell cytometry experiment because of lack of related instrument in our lab at that time. For further confirm the scientificity of our study, we have repeated most of experiments in this study when we found the query from editor, including cell cytometry, and the results had sent to the Journal (v.doria@verduci.it) two weeks ago. The repeated results had the consistent conclusion with the original article. ![file] ![file] , 
 Via http: www.most.gov.cn zxgz kycxjs kycxgzdt 202203 t20220318_179892.html u3000u30005. The paper  Effects of miR-214 on cervical cancer cell proliferation, apoptosis and invasion via modulating PI3K Akt mTOR signal pathway with Liu Qian as the corresponding author and Wang Fei as the first author of the Second Affiliated Hospital of Harbin Medical University. After investigation, the paper has tampered with the data. Faye Wong was dealt with as follows: admonishment of scientific research integrity, cancellation of application for scientific and technological plans (special projects, funds, etc.) projects and awards for 5 years, cancellation of qualification for promotion of postgraduate tutor for 4 years, and cancellation of qualification for promotion of professional title for 3 years; the following treatment was made to Liu Qian : The scientific research integrity admonition conversation, the cancellation of the application for scientific and technological plans (special projects, funds, etc.) projects and the qualification for awarding for 3 years, and the cancellation of the qualification for admission to academic degree graduate students for 3 years. ,