MicroRNA‚Ä?48 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K/AKT signalling pathway
Authors: Nanping Ai
Jingxue Zhang
Qian Liu
Shen Wu
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: Retinoblastoma; microRNAs; miR-448; cell proliferation; apoptosis
Affiliations: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing 100730, P.R. China., Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Abstract:  Retinoblastoma (RB) is the most common primary intraocular malignancy during infancy and childhood worldwide. Numerous microRNAs (miRNAs) contribute to RB initiation and progression through the regulation of cell proliferation, cycle, apoptosis, migration, invasion and metastasis. Therefore, further investigation concerning the expression, roles and associated mechanisms of RB‚Äërelated miRNAs may be beneficial to develop novel strategies for patients with this malignancy. Recently, miRNA‚Ä?48 (miR‚Ä?48) has been reported to be aberrantly expressed and to play an important role in several types of human cancer. However, the expression patterns and biological roles of miR‚Ä?48 in RB have not been studied. The aim of the present study was to detect the expression levels of miR‚Ä?48 and investigate its functions in RB and its associated molecular mechanisms. In the present study, miR‚Ä?48 was significantly downregulated in RB tissues and cell lines. Upregulation of miR‚Ä?48 decreased cell proliferation and invasion and increased apoptosis in RB cells. Additionally, œÅ‚Äëassociated coiled‚Äëcoil containing protein kinase 1 (ROCK1) was validated as a novel direct target gene of miR‚Ä?48 in RB. ROCK1 was overexpressed in RB tissues and inversely correlated with miR‚Ä?48 expression. Furthermore, ROCK1 silencing induced effects on the proliferation, invasion and apoptosis of RB cells similar to those observed following miR‚Ä?48 overexpression. Moreover, restoration of miR‚Ä?48 expression markedly reversed the effects of miR‚Ä?48 overexpression on RB cells, further supporting the hypothesis that ROCK1 is a direct functional target of miR‚Ä?48 in RB. Importantly, miR‚Ä?48 targeted ROCK1 to inhibit the activation of the PI3K/AKT signalling pathway in RB. These results demonstrated that miR‚Ä?48 may serve as a tumour suppressor in RB by directly targeting ROCK1 and regulating the PI3K/AKT signalling pathway, thereby suggesting that miR‚Ä?48 may be an effective therapeutic target for treating this aggressive cancer. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 5D, 6D.  Y79 and WERI-RB-1 cells were transfected with miR-448 mimics or miR-NC. After 48 h of transfection, the apoptosis rate was detected using flow cytometric analysis ;  flow cytometric analysis (D) were employed to examine the ... apoptosis rates in the indicated cells ;  ...apoptosis (D) were determined in the indicated cells  Pink rectangle to emphasise the similarity of one panel with one from Figs 2D, 5D, 6D of [Zhang et al (2018)] .  The match is not exact, but the two panels share enough points to suggest that they are derived from the same data file, plotted with different filters. Here at right, the version from Zhang et al is superimposed on the version from Wu et al, after a black white reversal so that shared points cancel out.  UPDATE: Blue-grey box: see matching panel in Figs 2D, 4D, 5D of [Zhao et al (2018)] .  -------------------------------------------- UPDATE #2: Rose box added.  Matches a panel of [Mao et al (2017)] .   , 
 #1 Pink-boxed panel is shared not only with [Zhang et al (2018)] , but also with Figs 2C, 4C, 5C of [Li et al (2019)] .  Another panel is also shared with Li et al (2019). Picked out with bright green boxes:  Here in context:   , 
 *[top]* Fig 5C from  MicroRNA-935 Inhibits Proliferation and Invasion of Osteosarcoma Cells by Directly Targeting High Mobility Group Box 1 ([Liu et al 2018] ). *[middle]* **Fig 6C**. *[bottom]* Fig 5C from  microRNAu2011574 inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting zinc finger Eu2011boxu2011binding homeobox 1 ([Mao et al 2018] ).  H t ImageTwin. , 
 *[top]* Fig 2C from  microRNAu2011574 inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting zinc finger Eu2011boxu2011binding homeobox 1 ([Mao et al 2018] ). *[middle]* **Fig 6C** again. *[bottom]* Fig 5E from  Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4 ([Wu et al 2020] ) **[retracted]**.  H t ImageTwin. , 
 While we re at it: *[left]* Fig 5C. *[right]* Fig 3A from  MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4 ([Mao et al 2017] .  , 
 #3 #4 ImageTwin wants me to point out that as well as the overlaps shown in those two comments, Fig 6C **also** overlaps with a panel in Fig 6C of  MicroRNA-454 inhibits the malignant biological behaviours of gastric cancer cells by directly targeting mitogen-activated protein kinase 1 ([Wang et al 2017] ) **[retracted]**.  , 
 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 from  MicroRNA-655 attenuates the malignant biological behaviours of retinoblastoma cells by directly targeting PAX6 and suppressing the ERK and p38u00efu00bfu00bdMAPK signalling pathways ([Zhang et al 2018] ). - **Fig 6C** again.  H t ImageTwin. , 
 *[above]* Fig 2C from  MicroRNAu201118b acts as an oncogene in gastric cancer by directly targeting Kruppelu2011like factor 6 ([Liu et al 2019] ). *[below]* The versatile Fig 6C **again**.  , 
 #1 Thanks to your team for discovering the relevant errors. In fact, in 2020, we have found that the relevant data and results of this paper cannot be repeated in the follow-up experiments, and questioned and discussed the actual results of this paper. And In January 2021, we reported the results to the journal that published the paper by email, and at the same time applied for the retraction of the paper. In view of the recent discovery of more image problems, we are also communicating with the magazine to complete the retraction of the manuscript as soon as possible. Thanks again for your work , 
 Retracted [20 June 2022] . Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that three data panels featured in the flow cytometric plots shown in Figs. 5D and 6D, and several panels from the cell invasion assays shown in Figs. 5C and 6C, 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 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. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,