AUTHOR=Dong Xubin , Akuetteh Percy David Papa , Song Jingjing , Ni Chao , Jin Cong , Li Huihui , Jiang Wenjie , Si Yuhao , Zhang Xiaohua , Zhang Qiyu , Huang Guanli 

TITLE=Major Vault Protein (MVP) Associated With BRAFV600E Mutation Is an Immune Microenvironment-Related Biomarker Promoting the Progression of Papillary Thyroid Cancer via MAPK/ERK and PI3K/AKT Pathways

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.688370

DOI=10.3389/fcell.2021.688370

ISSN=2296-634X

ABSTRACT=<p>Papillary thyroid cancer (PTC) is the most common malignancy of the endocrine system, with an increase in incidence frequency. Major vault protein (<italic>MVP</italic>) is the main structural protein of the vault complex that has already been investigated in specific cancers. Yet the underlying biological functions and molecular mechanisms of <italic>MVP</italic> in PTC still remain considerably uncharacterized. Comprehensive analyses are predicated on several public datasets and local RNA-Seq cohort. Clinically, we found that <italic>MVP</italic> was upregulated in human PTC than in non-cancerous thyroid tissue and was correlated with vital clinicopathological parameters in PTC patients. <italic>MVP</italic> expression was associated with <italic>BRAF</italic><sup>V600E</sup>, <italic>RAS</italic>, <italic>TERT</italic>, and <italic>RET</italic> status, and it was correlated with worse progression-free survival in PTC patients. Functionally, enrichment analysis provided new clues for the close relationship between <italic>MVP</italic> with cancer-related signaling pathways and the immune microenvironment in PTC. In PTC with high <italic>MVP</italic> expression, we found CD8<sup>+</sup> T cells, regulatory T cells, and follicular helper T cells have a higher infiltration level. Intriguingly, <italic>MVP</italic> expression was positively correlated with multiple distinct phases of the anti-cancer immunity cycle. <italic>MVP</italic> knockdown significantly suppressed cell viability and colony formation, and promoted apoptosis. In addition, downregulated <italic>MVP</italic> markedly inhibited the migration and invasion potential of PTC cells. The rescue experiments showed that <italic>MVP</italic> could reverse the level of cell survival and migration. Mechanistically, <italic>MVP</italic> exerts its oncogenic function in PTC cells through activating PI3K/AKT/mTOR and MAPK/ERK pathways. These results point out that <italic>MVP</italic> is a reliable biomarker related to the immune microenvironment and provide a basis for elucidating the oncogenic roles of <italic>MVP</italic> in PTC progression.</p>