MicroRNA-655 attenuates the malignant biological behaviours of retinoblastoma cells by directly targeting PAX6 and suppressing the ERK and p38ï¿½MAPK signalling pathways
Authors: Gang Liu
Hui Yin
Min Zhang
Qiongxia Li
Hui Wang
Yingzhe Pan
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: miRNA-655; retinoblastoma; PAX6; tumour-suppressor; oncogenes
Affiliations: Department of Ophthalmology, Xiangyang No. 1 People's Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China., Endoscopy Center, Xiangyang No. 1 People's Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China.

Abstract:  Numerous studies have indicated that microRNAs (miRNAs) regulate signalling molecules by acting as oncogenes or tumour-suppressor genes in retinoblastoma (RB). Therefore, investigation of the expression pattern, biological roles and associated mechanisms of cancer-related miRNAs in RB may provide novel therapeutic targets for patients with this disease. miRNA-655 (miR-655) has been reported to be aberrantly expressed in many types of cancers. However, the expression pattern, detailed biological function and underlying molecular mechanisms of miR-655 in RB remain to be clarified. Therefore, the aims of the present study were to detect miR-655 in RB, investigate its biological roles in RB and determine the underlying molecular mechanisms. The results of the present study showed that miR-655 was significantly downregulated in RB tissues and cell lines. Overexpression of miR-655 inhibited the proliferation and invasion ability while it increased the apoptosis of RB cells. Additionally, paired box 6 (PAX6) was identified as a direct target of miR-655 in RB. Furthermore, PAX6 was highly expressed in RB tissues and was negatively correlated with miR-655 expression. PAX6 knockdown recapitulated effects similar to those observed following miR-655 overexpression regarding the proliferation, invasion and apoptosis of RB cells. Rescue experiments demonstrated that restoration of PAX6 expression reversed the tumour-suppressing roles of miR-655 in RB cells. Moreover, upregulation of miR-655 reduced activation of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways in RB cells through PAX6 regulation. Therefore, restoration of miR-655 expression may be a promising therapeutic strategy for treating patients with RB in the future. 

Retracted: No

PubPeer comments:
 Figs 2D, 5D, 6D.  Flow cytometric analysis was used to evaluate the effect of miR-655 on the apoptosis of Y79 and WERI-RB-1 cells ;  Apoptosis rates of Y79 and WERI-RB-1 cells transfected with PAX6 siRNA or NC siRNA were examined using flow cytometric analysis ;  The apoptosis rate in each group was determined using flow cytometric analysis . ![file] Could the authors comment on the appearance of one panel (brown rectangle) in Figs 3B and 5D of [Shen et al (2018)] ?  Downregulation of miR-147 promotes the rate of the 5-FU-induced apoptosis in AGS and BGC-823 cells ;  The rate of 5-FU-induced apoptosis in the indicated cells was evaluated using flow cytometry analysis. ![file] UPDATE: Light-brown rectangle added, to mark a panel s reappearance in Fig 2C of [Lyu et al (2019)] . ![] Pink rectangle to mark a panel s reappearance in Fig 2D,5D,6D of [Wu et al (2018)] . ![file] ------------------------------------------------ UPDATE. I ran out of colors to mark panels, so I will just point out another match between one panel of this paper and another of [Zhao et al (2018)] . ![file] , 
 Figs 2D, 5D, 6D again. ![file] One panel also appears in Figs 2C, 5C, 6C from [Yao et al (2018)] . ![file] Shown here in context. ![file] , 
 #1 Pink-boxed panel is shared not only with [Wang et al (2018)] , but also with Figs 2C, 4C, 5C of [Li et al (2019)] . ![] , 
 ![] Lilac box marks panel shared with Figs 2D, 6D, 7D of [Deng et al (2018)] . ![] Here in context. ![] , 
 *[upper left]* Fig 6D E from  MicroRNAu2011876u20115p inhibits the progression of glioblastoma multiforme by directly targeting Forkhead box M1 ([Wang et al 2018] ). *[upper right]* **Fig 2C**. *[below]* Fig 5D E from  MicroRNAu2011466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin ([Jia et al 2018] ). ![file] , 
 *[top]* Fig 2C from  MicroRNA-935 Inhibits Proliferation and Invasion of Osteosarcoma Cells by Directly Targeting High Mobility Group Box 1 ([Liu et al 2018] ). *[middle]* **Fig 2C**. *[bottom]* Fig 3B from  MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4 ([Mao et al 2017] ). ![] H t ImageTwin , 
 A panel has been triplicated across three papers. - Fig 5D from  MicroRNAu2011874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin ([Zhang et al 2018a] ). - Fig 2C from  MicroRNAu2011598 inhibits the proliferation and invasion of nonu2011small cell lung cancer cells by directly targeting ZEB2 ([Tong et al 2018] ). - **Fig 5C**. ![file] , 
 Red and blue boxes indicate overlapping panels that link papers with otherwise-unrelated teams of authors. - Fig 5C from  MicroRNA-744 Inhibits Cellular Proliferation and Invasion of Colorectal Cancer by Directly Targeting Oncogene Notch1 ([Shen Li 2018] ). - **Fig 6C**. - Fig 6C from  MicroRNAu2011448 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K AKT signalling pathway ([Wu et al 2018] ). ![] H t ImageTwin. , 
 Retracted [8 August 2022] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that data shown in various of the panels portraying the results from flow cytometric experiments in Fig. 2D, 5D and 6D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. ,