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

Research Paper

MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9

Yang Liu1*, Siyuan Xu1*, Ying Huang1, Shaoyan Liu1, Zhengang Xu1, Minghui Wei2✉, Jie Liu1✉

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.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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. Available from https://www.ijbs.com/v17p3401.htm

File import instruction

Abstract

Graphic 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