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Forkhead box M1 transcription factor: a novel target for pulmonary arterial hypertension therapy

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Abstract

Background

Forkhead box M1 (FoxM1), a member of forkhead family, plays a key role in carcinogenesis, progression, invasion, metastasis and drug resistance. Based on the similarities between cancer and pulmonary arterial hypertension, studies on the roles and mechanisms of FoxM1 in pulmonary arterial hypertension have been increasing. This article aims to review recent advances in the mechanisms of signal transduction associated with FoxM1 in pulmonary arterial hypertension.

Data sources

Articles were retrieved from PubMed and MEDLINE published after 1990, including—but not limited to—FoxM1 and pulmonary arterial hypertension.

Results

FoxM1 is overexpressed in pulmonary artery smooth muscle cells in both pulmonary arterial hypertension patients and animal models, and promotes pulmonary artery smooth muscle cell proliferation and inhibits cell apoptosis via regulating cell cycle progression. Multiple signaling molecules and pathways, including hypoxia-inducible factors, transforming growth factor-β/Smad, SET domain-containing 3/vascular endothelial growth factor, survivin, cell cycle regulatory genes and DNA damage response network, are reported to cross talk with FoxM1 in pulmonary arterial hypertension. Proteasome inhibitors are effective in the prevention and treatment of pulmonary arterial hypertension by inhibiting the expression and transcriptional activity of FoxM1.

Conclusions

FoxM1 has a crucial role in the pathogenesis of pulmonary arterial hypertension and may represent a novel therapeutic target. But more details of interaction between FoxM1 and other signaling pathways need to be clarified in the future.

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Acknowledgements

We thank Prof. Ling Gu for insightful discussions and for the critical reading of this manuscript, and Dr. Xia Guo for language help.

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No external funding was secured for this paper.

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Authors and Affiliations

  1. Department of Pediatric Pneumology, West China Second University Hospital, Sichuan University, Chengdu, China

    Li Gu & Han-Min Liu

  2. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Wuhou District, Chengdu, China

    Li Gu & Han-Min Liu

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LG contributed to literature review and drafting. HML contributed to concept and design, and critical revision. Both authors approved the final version of the manuscript.

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Correspondence to Han-Min Liu.

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Gu, L., Liu, HM. Forkhead box M1 transcription factor: a novel target for pulmonary arterial hypertension therapy. World J Pediatr 16, 113–119 (2020). https://doi.org/10.1007/s12519-019-00271-1

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