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Horm Metab Res 2023; 55(02): 149-155
DOI: 10.1055/a-1981-3328
Original Article: Endocrine Research

Transcription Factor ELK3 Promotes Stemness and Oxaliplatin Resistance of Glioma Cells by Regulating RNASEH2A

Yimin Mei
1   Neurosurgery, Zhejiang Lishui Central Hospital, Lishui, China
,
Duoning Chen
1   Neurosurgery, Zhejiang Lishui Central Hospital, Lishui, China
,
Shike He
1   Neurosurgery, Zhejiang Lishui Central Hospital, Lishui, China
,
Jinping Ye
1   Neurosurgery, Zhejiang Lishui Central Hospital, Lishui, China
,
Ming Luo
1   Neurosurgery, Zhejiang Lishui Central Hospital, Lishui, China
,
Qiangjun Wu
1   Neurosurgery, Zhejiang Lishui Central Hospital, Lishui, China
,
Yuan Huang
2   Pathology, Zhejiang Lishui Central Hospital, Lishui, China
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Abstract

Oxaliplatin is a member of the platinum group that is often used to treat glioma, a common type of malignant brain tumor, though it does not come with desirable and notable effects. This study attempted to investigate how ELK3 impacts the oxaliplatin resistance of glioma cells and its molecular mechanism. Bioinformatics analysis was employed to screen mRNAs with differential expression in glioma cells and predict the possible regulator downstream. We used qRT-PCR to detect the expression of ELK3 and RNASEH2A. Dual-luciferase and ChIP assays were adopted to reassure the regulatory relationship between the two. We also evaluated cell viability and sphere formation efficiency through CCK-8 and sphere formation assay and calculated the IC50 value by using CCK-8 assay. The expression of stemness-related proteins (ALDH1 and Nanog) was assessed through western blot. Glioma cells and tissues presented a significantly high expression of ELK3, the knock-down of which would reduce the cell viability, stemness and oxaliplatin resistance dramatically. Bioinformatics analysis predicted RNASEH2A to be the downstream regulator of ELK3. RNASEH2A was remarkably upregulated in glioma tissue and cells. The results from dual luciferase assay and ChIP experiment verified the binding relationship between RNASEH2A promoter region and ELK3. Then through rescue experiments, we confirmed that overexpression of RNASEH2A could compensate for the inhibition of glioma cell progression resulting from the knock-down of ELK3. ELK3 could promote stemness and oxaliplatin resistance of glioma cells by upregulating RNASEH2A, indicating that targeting ELK3/RNASEH2A axis may be a possible solution to overcome oxaliplatin resistance of glioma cells.

Key words

ELK3 - RNASEH2A - glioma cells - tumor cell stemness - oxaliplatin resistance

Supplementary Material



Publikationsverlauf

Eingereicht: 16. August 2022

Angenommen nach Revision: 09. November 2022

Artikel online veröffentlicht:
13. Januar 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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