Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4
Authors: Xin Wan
Dongxu Qiu
Jing Li
Zhongyi Sun
Xiao Jiao
Ronghe Yang
Jun Deng
Zhiwei Xia
Journal: International Journal of Molecular Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-98; glioma; DNA methylation; 5-Aza-20-deoxycytidine
Affiliations: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China., Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Abstract:  MicroRNAs (miRs) have been found to play key roles in various human cancers, but the detailed regulatory mechanism of miR-98 in glioma remains largely unknown. The findings of the present study demonstrated that miR-98 was frequently downregulated in glioma tissues and cell lines (U87, U251, U373 and SHG44), and the decreased miR-98 levels were associated with DNA methylation. Treatment with 5-Aza-20-deoxycytidine, a DNA methyltransferase inhibitor, significantly increased the expression of miR-98 in glioma cells. Moreover, both miR-98 downregulation and methylation were significantly associated with a more aggressive tumor phenotype in glioma, as well as shorter survival time of glioma patients. Restoration of miR-98 expression caused a marked decrease in the migration and invasion of U87 cells, but did not affect cell proliferation. Sal-like protein 4 (SALL4) was further identified as a novel target gene of miR-98, and its protein expression was negatively regulated by miR-98 in U87 cells. Restoration of SALL4 expression reversed the suppressive effects of miR-98 on the migration and invasion of U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and an inverse correlation between miR-98 and SALL4 expression in glioma tissues was identified. In addition, the increased expression of SALL4 was significantly associated with glioma progression. Taken together, these data demonstrated that downregulation of miR-98, induced by methylation, promotes glioma cell migration and invasion via targeting SALL4. Therefore, miR-98 may become a potential therapeutic candidate for glioma. 

Retracted: Yes

PubPeer comments:
 Figs 4D, 6D.  ...Transwell assay were conducted to evaluate cell ... invasion. ![file] I set up a spreadsheet to include the various papers using this versatile suite of Transwell images to represent all possible combinations of cell-lines and treatments. This is the 21th manifestation. For comparison: Fig 3 C D from [Zhang et al (2016)] .  Transwell assay were performed to examine the migratory and invasive capacities of Saos-2 and U2OS cells transfected with miR-205 mimic or miR-negative control (NC) mimic , and Fig 7C D,  Transwell assay were performed to examine cell migration and invasion of MG63 or U2OS cells transfected with miR-205 mimic, or co-transfected with miR-205 mimic and RUNX2 plasmid . ![] Also *[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 . ![file] , 
 Fig 6C (Wound healing assay). The two 0-hour panels are repeated with a 180-deg flip: marked with red rectangles. ![file] More concerning are the overlaps with Fig 7A of [Zhong et al (2018)] ,  Wound-healing assays , marked with violet and orange. The 0-Hour Panels in 7A seem to be the same (bright green rectangles). ![file] Also overlaps with U251 panels of Fig 4D of [Jiang et al (2018)] . ![file] , 
 Retracted [17 May 2021] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 4D and 6D) were strikingly similar to data appearing in different form in other articles by different authors at different research institutions, which were already under consideration for publication or had already been published elsewhere at the time of the present article s submission.  Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to International Journal of Molecular Medicine, 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. --------------------------------------------------- Background [here] . ,