Cancer Metabolism

Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention

Abstract

Background

3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC).

Methods

The transcription and protein expression of BDH2 in NPC were determined by both real-time RT-PCR and immunohistochemistry staining assays. Cell proliferation, migration and invasion were evaluated by MTT assay, wound-healing assay and Transwell assay, respectively. The profile of genes regulated by restoring BDH2 expression in NPC cells was analysed by cDNA microarray. The level of iron in NPC cells was detected by iron colorimetric assay.

Results

The expression of BDH2 was significantly downregulated in NPC. Ectopic expression of BDH2 inhibited NPC cell proliferation and colony formation. Meanwhile, BDH2 suppressed the migration and invasion of NPC cells by reversing the epithelial–mesenchymal transition (EMT). In addition, a higher level of BDH2 decreased the growth and metastasis of NPC cells via reducing intracellular iron level.

Conclusions

Our findings suggest that BDH2 may be a candidate tumour-suppressor gene in NPC. Decreasing intracellular iron could be an effective therapeutic approach for NPC.

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Acknowledgements

We thank Dr. Liudmila Matskova (Institute of Living Systems, Immanuel Kant Baltic Federal University, Kaliningrad, Russia) for his useful comment.

Author information

Z.Z., R.S.W. and X.Y.Z. were involved in the design of the project. B.L., Z.P.L., Y.X.M., C.P.D., S.H.Z. and Y.S.L. were involved in performing experiments and collecting data. W.L.Z., X.L.X., W.M.C., F.G.F. and X.H.Z. were involved in analysis and interpretation of data. X.X., P.L. and G.W.H. were involved in the acquisition of clinical samples. All authors have contributed to the writing of the paper and have critically reviewed it.

Correspondence to Rensheng Wang or Zhe Zhang.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Research Ethics Committee of Guangxi Medical University (Nanning, China). Written informed consent was obtained from all patients. All methods were performed in accordance with the relevant guidelines and regulations. Animal experimental procedures were performed under protocol No. 201808022, approved and regulated by The Animal Care & Welfare Committee of Guangxi Medical University. The study was performed in accordance with the Declaration of Helsinki.

Funding

This work was supported by the National Natural Science Foundation of China (81772882, 81660458) and Promotion of Basic Ability of Young and Middle-aged Teachers in Universities in Guangxi (KY2016YB080).

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All authors read and consented to publication of the paper.

Data availability

The microarray data have been deposited to the NCBI-GEO database (https://www.ncbi.nlm.nih.gov/geo/) with the data set identifier GSE119642.

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Li, B., Liao, Z., Mo, Y. et al. Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention. Br J Cancer 122, 102–110 (2020). https://doi.org/10.1038/s41416-019-0638-8

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