Knockdown of HNRNPM inhibits the progression of glioma through inducing ferroptosis

ABSTRACT

Purpose

Ferroptosis acts as an important regulator in diverse human tumors, including the glioma. This study aimed to screen potential ferroptosis-related genes involved in the progression of glioma.

Materials and Methods

Differently expressed genes (DEGs) were screened based on GSE31262 and GSE12657 datasets, and ferroptosis-related genes were separated. Among the important hub genes in the protein-protein interaction networks, HNRNPM was selected as a research target. Following the knockdown of HNRNPM, the viability, migration, and invasion were detected by CCK8, wound healing, and transwell assays, respectively. The role of HNRNPM knockdown was also verified in a xenograft tumor model in mice. Immunohistochemistry detected the expression levels of HNRNPM and Ki67. Moreover, the ferroptosis was evaluated according to the levels of iron, glutathione peroxidase (GSH), and malondialdehyde (MDA), as well as the expression of PTGS2, GPX4, and FTH1.

Results

Total 41 overlapping DEGs relating with ferroptosis and glioma were screened, among which 4 up-regulated hub genes (HNRNPM, HNRNPA3, RUVBL1, and SNRPPF) were determined. The up-regulation of HNRNPM presented a certain predictive value for glioma. In addition, knockdown of HNRNPM inhibited the viability, migration, and invasion of glioma cells in vitro, and also the tumor growth in mice. Notably, knockdown of HNRNPM enhanced the ferroptosis in glioma cells. Furthermore, HNRNPM was positively associated with SMARCA4 in glioma.

Conclusions

Knockdown of HNRNPM inhibits the progression of glioma via inducing ferroptosis. HNRNPM is a promising molecular target for the treatment of glioma via inducing ferroptosis. We provided new insights of glioma progression and potential therapeutic guidance.

KEYWORDS:

• Glioma
• HNRNPM
• ferroptosis
• bioinformatics analysis
• SMARCA4

Authors’ contributions

Conceptualization: Jian Wang and Xiaolin Luo

Formal analysis: Jian Wang, Xiaolin Luo and Dehua Liu

Investigation: Jian Wang and Xiaolin Luo

Methodology: Dehua Liu

Writing – original draft: Jian Wang, Xiaolin Luo and Dehua Liu

Writing – review & editing: Jian Wang and Xiaolin Luo

Approval of final manuscript: all authors

Data availability statement

The datasets generated and/or analyzed during the current study are not publicly available due [Gannan Medical University] but are available from the corresponding author on reasonable request

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

All experimental protocols were approved by the Animal Ethics Committee of Gannan Medical University.

All methods were carried out in accordance with the Guide for the Care and Use of Laboratory Animals.

All methods are reported in accordance with ARRIVE guidelines for the reporting of animal experiments. The study was carried out in accordance with the relevant guidelines and regulation.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2286782

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.