MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9

Liu, Yang; Xu, Siyuan; Huang, Ying; Liu, Shaoyan; Xu, Zhengang; Wei, Minghui; Liu, Jie

doi:10.7150/ijbs.60628

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Theranostics

International Journal of Medical Sciences

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Int J Biol Sci 2021; 17(13):3401-3412. doi:10.7150/ijbs.60628 This issue Cite

Research Paper

MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9

Yang Liu^1*, Siyuan Xu^1*, Ying Huang¹, Shaoyan Liu¹, Zhengang Xu¹, Minghui Wei^2✉, Jie Liu^1✉

1. Department of Head and Neck Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
2. Department of Head and Neck Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, P. R. China.
*These authors contributed equally to this work.

Citation:

Liu Y, Xu S, Huang Y, Liu S, Xu Z, Wei M, Liu J. MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9. Int J Biol Sci 2021; 17(13):3401-3412. doi:10.7150/ijbs.60628. https://www.ijbs.com/v17p3401.htm

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Abstract

Membrane-associated ring-CH-type finger (MARCH) proteins belong to the E3 ubiquitin ligase family, which regulates protein stability by increasing ubiquitination. Recent evidence has shown that some MARCH proteins play important roles in cancer development. However, the role of MARCH6 in tumorigenesis, including thyroid tumorigenesis, remains unknown. In this study, we determined that MARCH6 was upregulated in the majority of primary papillary thyroid cancers (PTCs) at both the mRNA and protein levels. Gain-of-function and loss-of-function studies demonstrated that MARCH6 suppressed apoptosis and promoted cell cycle progression, cell proliferation, growth, migration and tumorigenesis in thyroid cancer cells. Mechanistically, MARCH6 interacted with and downregulated DHX9. Knockdown of DHX9 enhanced the proliferative and migratory abilities of thyroid cancer cells. The inhibitory effect of MARCH6 knockdown on thyroid cancer cell growth and migration was also reversed by DHX9 silencing. In addition, MARCH6 activated the AKT/mTOR signaling pathway in a manner dependent on the downregulation of DHX9. Overall, MARCH6 functions as a potential oncogene in thyroid cancer by destabilizing DHX9 and activating AKT/mTOR signaling.

Keywords: Papillary thyroid cancer, MARCH6, Tumorigenesis, DHX9, AKT/mTOR

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APA

Liu, Y., Xu, S., Huang, Y., Liu, S., Xu, Z., Wei, M., Liu, J. (2021). MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9. International Journal of Biological Sciences, 17(13), 3401-3412. https://doi.org/10.7150/ijbs.60628.

ACS

Liu, Y.; Xu, S.; Huang, Y.; Liu, S.; Xu, Z.; Wei, M.; Liu, J. MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9. Int. J. Biol. Sci. 2021, 17 (13), 3401-3412. DOI: 10.7150/ijbs.60628.

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CSE

Liu Y, Xu S, Huang Y, Liu S, Xu Z, Wei M, Liu J. 2021. MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9. Int J Biol Sci. 17(13):3401-3412.

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