miR-484 suppresses proliferation and epithelial–mesenchymal transition by targeting ZEB1 and SMAD2 in cervical cancer cells
Authors: Hua Tang
Weiying Liu
Yankun Liu
Hong Xie
Yang Hu
Min Liu
Journal: Cancer Cell International (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cervical cancer; EMT; SMAD2; ZEB1; miR-484.
Affiliations: Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070 China.

Abstract:  Background: MicroRNAs (miRNAs) play important roles in cancer initiation and development. Epithelial-mesenchymal transition (EMT) is a form of cellular plasticity that is critical for embryonic development and metastasis. The purpose of the study was to determine the function and mechanism of miR-484 in initiation and development of cervical cancer (CC). Methods: We determined the expression levels of miR-484 in cervical cancer tissues and cell lines with RT-qPCR. Prediction algorithms and EGFP reporter assay were performed to evaluate the targets for miR-484. MTT assay, colony formation assay, flow cytometric analysis, transwell cell migration and invasion assays, and detection of EMT markers were employed to investigate the roles of miR-484 and the targets in regulation of cell proliferation and EMT process. We also used rescue experiments to confirm the effect of miR-484 on CC cells through directly regulating the expression of its targets. Results: Firstly we found miR-484 was down-regulated in cervical cancer tissues and cell lines compared with their matched non-cancerous tissues or normal cervical keratinocytes cells. Further studies revealed that overexpression of miR-484 suppressed the cell proliferation, while exacerbates apoptosis. Besides, miR-484 suppressed cellular migration, invasion and EMT process of CC cells. EGFP reporter assay showed that miR-484 binds to ZEB1 and SMAD2 3'UTR region and reduced their expression. The expression of miR-484 had reverse correlation with SMAD2/ZEB1, and SMAD2/ZEB1 had positive correlation with each other in cervical cancer tissues and cell lines. Furthermore, the ectopic expression of ZEB1 or SMAD2 could rescue the malignancies suppressed by miR-484, suggesting that miR-484 down-regulates ZEB1 and SMAD2 to repress tumorigenic activities. Conclusion: We found miR-484 inhibits cell proliferation and the EMT process by targeting both ZEB1 and SMAD2 genes and functions as a tumor suppressor, which may served as potential biomarkers for cervical cancer. 

Retracted: No

PubPeer comments:
 Figures 5A and 5B appear to have two images which overlap. *** ![file] *** ![file] , 
 Dear Actinopolyspora Biskrensis, Thank you very much for pointing out this error. We checked the data, the transwell invasion image for ASO-NC of HeLa cell in Fig. 3B was wrongly placed by mistake during the preparation of the figure. The corrected version of Fig. 3 A,B (not 5A, B) and Fig. 3 were provided below. This correction does not change the conclusions of this paper. The authors regret in the original version of the article and will make the corrigendum. We apologize for this mistake due to our carelessness. Best regards, Yang Hu Hua Tang ![file] ![file] , 
 Dear Dr. Tang, Thank you for addressing the duplication marked with red boxes in #1. Could you also check some additional duplications in Figures 3A, 3B, 7A, and 7B, please? I have marked those here with boxes of the same color. The one marked in red is the one you already addressed. ![file] , 
 Retracted [10 May 2021] . ------------------------ The Editors-in-Chief have retracted this article [1]. Concerns were raised regarding a number of figures, specifically: - Figure 3a: the first and third panel for C33A appear to partially overlap. - Figure 3b: panel 2 for C33A appears to partially overlap with panel 2 for C33A in Figure 7b. - Figure 7a: panel 1 for HeLa appears to overlap with panel 3 for HeLa in Figure 7b. - Figure 7a: panel 3 for C33A appears to partially overlap with panels 4 and 4 for C33A in Figure 7b: panel 6 for HeLa appears to partially overlap with panel 5 for C33A. The Editors-in-Chief therefore no longer have confidence in the reliability of the data reported in the article. All authors agree to this retraction. , 
 **Decisions on handling scientific research misconduct cases investigated and dealt with in 2022 (first batch)** Date 2022-05-13 Source: u3000 Author: u3000 u3010 Large, Middle and Small u3011 u3010Printu3011 u3010Closeu3011 u3000u3000The National Natural Science Foundation of China resolutely implements the spirit of the  Several Opinions on Further Strengthening the Construction of Scientific Research Integrity and  Opinions on Further Promoting the Spirit of Scientists and Strengthening the Construction of Style and Study Style by the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council. Horizontal science and technology are self-reliant and self-reliant, continue to carry out scientific research integrity construction, and seriously investigate and deal with scientific research misconduct involving the National Natural Science Foundation of China. The Supervision Committee of the National Natural Science Foundation of China conducts investigations, verifications and comprehensive judgments on the accepted scientific research integrity cases, in accordance with the Regulations of the National Natural Science Foundation of ) and  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China and other regulations and systems to propose handling suggestions. After deliberation at the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to deal with the relevant parties involved. The 10 handling decisions (online release version) that have been criticized and criticized are hereby announced. -------------------------------- **Decision on the handling of problems such as improper manipulation of images, confusion of experimental data, and false information in project applications, progress reports and final reports published by Tang Hua et al.** - National Science and Technology Financial Supervisory Office [2022] No. 2 The Supervision Committee of the National Natural Science Foundation of China launched an investigation into the papers published by Tang Hua and others of Tianjin Medical University for suspected academic misconduct. The papers involved are as follows: ... u3000u3000Paper 24:  Yang Hu, Hong Xie, Yankun Liu, Weiying Liu, Min Liu, Hua Tang*. **miR-484 suppresses proliferation and epithelial- mesenchymal transition by targeting of ZEB1 and SMAD2 in cervical cancer cells**. Cancer Cell International. 2017, 17(1): 36.u201d (marked with fund numbers 91029714, 31270818, 81572790) ... u3000u3000According to the investigation of the supporting unit, the above paper has problems such as improper operation of pictures and confusion of experimental data. The corresponding author Tang Hua is mainly responsible for the above problems. In addition, Tang Hua has included the above papers in his 7 National Natural Science Foundation of China projects (approval numbers 30873017, 91029714, 31071191, 31270818, 81572790, 91629302, 81830094) applications, progress reports, and final reports. Responsible for the objective results of false information in the project application, progress report or final report. u3000u3000After deliberation at the 12th meeting of the Fifth Session of the Supervision Committee of the National Natural Science Foundation of China (Life Medicine Professional Committee), and the approval of the 2nd Executive Meeting of the National Natural Science Foundation of China in 2022, it was decided to follow the thirty-fifth National Natural Science Foundation of China Regulations. Item 4 of Article 4, Item 2 of Article 16 and Item 3 of Article 17 of  Measures for Handling Misconduct in Science Fund Funding Work by the Supervision Committee of the National Natural Science Foundation of China (for Trial Implementation) , revocation of Tang Hua National Natural Science Foundation of China Science Fund Projects  Research on the molecular mechanism of Hsa-miR-10a inhibiting colon cancer metastasis (Grant No. 30873017),  Research on the interaction between miRNA and TNF-u03b1-IKK-NF-u03baB signaling pathway genes in ovarian cancer cells (Approval No. 91029714),  Research on the mechanism of miR-372 regulating the cycle of cervical cancer cells (Approval No. 31071191),  Regulation of Ago2 stability by PSMC3 and its mechanism (Approval No. 31270818),  miR-372 in liver cancer cells Epigenetic regulation and functional mechanism of 615-5pu201d (Grant No. 81572790), u201cThe mechanism of inflammatory factors activating NF-u03baB STAT3 to regulate the malignant behavior of tumor cells and the formation of pre-metastatic microenvironment through epigenetic modificationu201d ( Approval No. 91629302),  Study on the role and mechanism of m6A-RNA mediated by HPVE6 E7 in cervical cancer cells mediated by METTL3 (approval No. 81830094), recover the funds allocated for the above 7 projects, cancel the Tanghua National Natural Science Foundation of China The Science Foundation project is eligible for 5 years (January 18, 2022 to January 17, 2027), and the criticism will be given to Tang Hua. - National Natural Science Foundation of China - March 30, 2022 ,