microRNA‚Ä?85 inhibits the malignant behaviors of retinoblastoma by directly targeting Wnt3a
Authors: Jia Lu
Hong Zhang
Ling Wang
Lina Wang
Xueman Lyu
Journal: Oncology Reports (2019)
Discipline: CLINICAL MEDICINE
Keywords: miRNA; retinoblastoma; miR-485-5p; deregulation; cancer
Affiliations: Department of Ophthalmology, China‚ÄëJapan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Abstract:  Deregulation of microRNAs (miRNAs) has been widely reported in retinoblastoma (RB), and the aberrantly expressed miRNAs may serve as crucial epigenetic regulators in the occurrence and development of RB. Therefore, the identification of dysregulated miRNAs in RB may be useful for the development of effective targets for the therapy patients with this disease. miRNA (miR)‚Ä?85‚Ä?p (miR‚Ä?85) is deregulated in multiple human cancer types and serves crucial roles in their progression and development. However, the expression pattern of miR‚Ä?85 and its role in RB have not been well investigated. In the present study, expression levels of miR‚Ä?85 in RB tissues and cell lines were measured using reverse transcription‚Äëquantitative polymerase chain reaction (RT‚ÄëqPCR). The effects of miR‚Ä?85 overexpression on RB cell proliferation, apoptosis, migration and invasion were examined using Cell Counting Kit‚Ä? assay, flow cytometric analysis and in vitro migration and invasion assays, respectively. Xenograft tumor formation assay was utilized to determine the influence of miR‚Ä?85 on RB tumor growth in vivo. The mechanism responsible for the tumor‚Äësuppressing roles of miR‚Ä?85 in RB progression was determined through a series of experiments, including bioinformatics prediction, luciferase reporter assay, RT‚ÄëqPCR, western blot analysis and rescue experiments. Herein, a marked downregulation of miR‚Ä?85 expression in human RB tissues and cell lines was observed. miR‚Ä?85 overexpression suppressed RB cell proliferation, induced cell apoptosis, attenuated cell migration and cell invasion in vitro, and restrained the growth of RB cells in vivo. Additionally, Wnt3a was revealed to be a direct target gene of miR‚Ä?85 in RB cells. Wnt3a was upregulated in human RB tissues, and its upregulation was inversely associated with miR‚Ä?85. Furthermore, the tumor suppressive roles of Wnt3a silencing were similar to those of miR‚Ä?85 overexpression in RB cells. In addition, restoration of Wnt3a expression partially reversed the tumor suppressor action of miR‚Ä?85 in RB cells. However, miR‚Ä?85 upregulation directly targeted Wnt3a to inhibit activation of the Wnt/Œ≤‚Äëcatenin signaling pathway in RB cells both in vitro and in vivo. Notably, these results demonstrated that the tumor‚Äësuppressive roles of miR‚Ä?85 were at least partially mediated by Wnt3a in RB cells. Therefore, miR‚Ä?85 is a potential therapeutic target for treating patients with RB. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4C, 5D.  Flow cytometric analysis was used to measure the percentage of apoptotic Y79 and Weri-RB1cells that were treated with miR-485 mimics or miR-NC ;  The apoptosis rate of aforementioned cells was detected using flow cytometric analysis ;  Protein expression of Wnt3a was measured by... flow cytometric analysis .  The panel of 2C marked with a light brown rectangle also appears in Fig 6D of [Zhang et al (2018)] .  Could the authors comment on this coincidence?  ----------------------------------------------------- UPDATE: Purple box marks a panel with a match in Figs 2D, 5D, 6D of [Zhao et al (2018)] .  , 
 #1 Figs 2C, 4C, 5D again.  Magenta box from lower left corner matches a panel from Figs 2D, 5D, 6E of [Wang et al (2019)] .  , 
 Figs 2C, 4C, 5D again.  One panel matches a panel from Figs 2C, 5C, 6C of [Cheng et al (2020)] , though the upper lower cut-off is at a different level.  UPDATE: Blue box marks a panel that also appears in Figs 2D, 6F, 7F of [Cui et al (2018)] .   , 
 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 .  Certain pairs of tumors appear to be the same (colored boxes). All five institutions seem to be using the same distinctively-battered ruler. , 
 Retracted [14 June 2022] .  Following the publication of the above paper, the authors submitted a request to the Editorial Office to retract the article on account of the fact that the ethical approval for the tumor xenograft experiments performed in mice, as shown in Fig. 7, had not been obtained from their hospital; consequently, all authors were in agreement that the article should be retracted to ensure the integrity of the scholarly record. Independently of this request, it was also drawn to the Editoru2019s attention by a concerned reader that data in several of the figures were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that there were contentious data in the above article that had already been published prior to its submission to *Oncology Reports*, and after assessing the authors request, the Editor concurs that this paper should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. ,