miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting <em>ZEB1</em>
Authors: Rui Yao
Liqun Wu
Pingsheng Cai
Huzhong Zheng
Journal: OncoTargets and Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: aggressive behaviors; microRNA-641; target therapy; zinc finger E-Box binding homeobox 1.
Affiliations: Department of Obstetrics and Gynecology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000, Zhejiang, People's Republic of China, .

Abstract:  Background: miRNAs have been found to be dysregulated in cervical cancer. The dysregulation of miRNA has been implicated in cervical carcinogenesis and progression. Therefore, further studies of the specific roles of deregulated miRNAs in cervical cancer and underlying molecular mechanisms may facilitate the identification of novel therapeutic techniques for patients with this disease. miRNA-641 (miR-641) was previously reported to serve an important role in lung cancer. However, the expression pattern and roles of miR-641 in cervical cancer remain unclear. Method: In this study, the expression level of miR-641 in cervical cancer tissues and cell lines was detected using RT-qPCR. The influence of miR-641 upregulation in cervical cancer cell proliferation, apoptosis, migration and invasion was evaluated using CCK-8 assay, flow cytometry assay, migration and invasion assays, respectively. In vivo tumor growth assay was utilized to determine the effect of miR-641 overexpression in the tumor growth of cervical cancer cells in vivo. The molecular mechanisms underlying the action of miR-641 in cervical cancer cells were also explored. Results: We found that miR-641 expression was obviously decreased in cervical cancer tissues and cell lines, which strongly correlated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Upregulation of miR-641 inhibited cell proliferation, induced apoptosis, and reduced metastasis in cervical cancer. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-641. Notably, luciferase reporter assay, RT-qPCR, and Western blot analysis revealed that miR-641 decreased ZEB1 expression in cervical cancer cells by directly targeting its 3'-untranslated region. Furthermore, ZEB1 was upregulated in cervical cancer tissues, which was negatively correlated with miR-641 expression. Moreover, recovered ZEB1 expression attenuated the tumor suppressive action of miR-641 overexpression in the malignant phenotypes of cervical cancer cells. Besides, miR-641 could hinder cervical cancer tumor growth in vivo by inhibiting ZEB1. Conclusion: These results indicate that miR-641 has tumor suppressive roles in the development of cervical cancer by directly targeting ZEB1, suggesting that miR-641 is a novel, effective therapeutic target for treating patients with this disease. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 5C, 6C. ![file] One panel also appears in Figs 2D, 5D, 6D from [Zhang et al (2018)] . ![file] Shown here in context. ![file] There may be other matches here, or with panels from other papers in this oeuvre. , 
 Clockwise from left: - Fig 7A from [Wang et al (2018)] .  The representative images of the miR-769 mimics and miR-NC [SW480] tumor xenografts. Rotated through 90 deg to facilitate comparison. - Fig 7B from [Song et al (2018)] .  Representative images of the miR-532 mimics and miR-NC [SW480] xenograft tumors . - Fig 7A from [Lv et al (2019)] .  The representative images of [HOS] tumor xenografts obtained from agomir-NC and agomir-761 groups . - **Fig 7A from [Lyu et al (2019)] **.  Representative images of the [Y79] tumor xenografts derived from miR-485 mimics or miR-NC groups . - Fig 7A from [Yao et al (2018)] .  Photographs of tumor xenografts derived from miR-641 mimics- or miR-NC-transfected HeLa cells . ![file] Certain pairs of tumors appear to be the same (colored boxes). All five institutions seem to be using the same distinctively-battered ruler. , 
 Retracted, [17 September 2021] . -------------------------------- The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2C and 7A with similar images from unrelated articles, specifically: - Figure 2C, panel SiHa miR-NC appears to have been duplicated with a similar image in Figure 5D from Zhang et al, 2018 . - Figure 7A, panel miR-NC appears to have been duplicated with a similar image in Figure 7A from Wang et al, 2018 . The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,