Demethylation drug 5-Aza-2‚Ä?deoxycytidine-induced upregulation of miR-200c inhibits the migration, invasion and epithelial-mesenchymal transition of clear cell renal cell carcinoma in vitro
Authors: Siqing Ding
Jian Sun
B O Yi
Juan Jiang
Wei Cao
Mengzi Liu
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: clear cell renal cell carcinoma; demethylation drug; epithelial-mesenchymal transition; invasion; microRNA-200c
Affiliations: Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China., Department of Nursing, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Abstract:  The microRNA (miR)-200 family has been found to be involved in the process of mesenchymal-epithelial transition during renal development. Deregulation of miR-200c has been suggested to be involved in clear cell renal cell carcinoma (ccRCC). However, the precise role of miR-200c in the regulation of ccRCC metastasis has not been previously reported. In the present study, it was observed that miR-200c was frequently downregulated in ccRCC tissue compared with matched adjacent normal tissue. The expression of miR-200c was additionally reduced in ccRCC cell lines when compared with levels in normal renal cells. The DNA demethylation drug 5-Aza-2'-deoxycytidine (Aza) was used to treat several ccRCC cell lines, and it was observed that the expression of miR-200c was significantly increased following Aza treatment. Furthermore, treatment with Aza markedly inhibited ccRCC cell invasion and migration, while treatment with miR-200c inhibitor significantly enhanced invasion and migration of ccRCC cells. In addition, Aza treatment significantly promoted expression of E-cadherin and inhibited the expression of N-cadherin, while the inhibition of miR-200c downregulated E-cadherin and upregulated the expression of N-cadherin, suggesting that miR-200c has a suppressive role in epithelial-mesenchymal transition (EMT) of ccRCC cells. In conclusion, it was suggested that demethylation drug Aza-induced upregulation of miR-200c may inhibit migration, invasion and EMT in ccRCC cells. 

Retracted: Yes

PubPeer comments:
 Fig 3A.  Cell migration assay was performed to determine cell invasion levels in ccRCC cells treated with Aza (10 nM) for 72 h .  Green rectangle highlights panel shared with Fig 4 of [Yang et al (2016)] .  . , 
 Figure 4.  Cell invasion assay was performed to determine cell invasion levels in Aza-treated clear cell renal cell carcinoma cells with or without transfection with miR-200c inhibitor .  I have color-coded these versatile panels to match *[above]* Fig 4C from [Lai, Chen Li (2015)] .  a Transwell assay were performed to examine the cell proliferation of AGS cells transfected with miR-133a mimics, miR-133a inhibitor, or co-transfected with miR-133a mimics and FSCN1 plasmid. Control: AGS cells without any transfection. *[below]* Figs 3(B), 6(B) from [Shi et al (2015)] .  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with NC scramble miRNA or miR-204 mimics, respectively. Control, Saos-2 and U-2 OS cells without any transfection ...  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with Sirt1 siRNA or co-transfected with miR-204 mimics and the Sirt1 plasmid, respectively. Control, Saos-2 and U-2 OS cells without any transfection .  , 
 #1 Apologies, wrong image for comparison. Try this:  Fig 4 of [Yang et al (2016a)] .  Fig 4B of [Yang et al (2016b)] .  Fig 7 (LOVO half) from [Tian et al (2015)] :  Fig 8 of [Li et al (2016)]  , 
 Retracted [14 July 2021] . --------------------------------- Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that certain of the scratchu2011wound assay data shown in Fig. 3A, and the Transwell cell migration assay data in Fig. 4, 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 Letters*, 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 any reply. The Editor apologizes to the readership for any inconvenience caused. ,