Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4 Retraction in /10.3892/ijmm.2021.4962

Xia,Zhiwei; Qiu,Dongxu; Deng,Jun; Jiao,Xiao; Yang,Ronghe; Sun,Zhongyi; Wan,Xin; Li,Jing

doi:10.3892/ijmm.2018.3464

Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4

Retraction in: /10.3892/ijmm.2021.4962

Authors:
- Zhiwei Xia
- Dongxu Qiu
- Jun Deng
- Xiao Jiao
- Ronghe Yang
- Zhongyi Sun
- Xin Wan
- Jing Li
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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
Published online on: February 6, 2018 https://doi.org/10.3892/ijmm.2018.3464
Pages: 2651-2659
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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