AUTHOR=Liu Hua , Chen Biao , Liu Lian-Lin , Cong Lin , Cheng Yong 

TITLE=The role of MARCH9 in colorectal cancer progression

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.906897

DOI=10.3389/fonc.2022.906897

ISSN=2234-943X

ABSTRACT=<p>Colorectal cancer (CRC) is the third most common cancer with a high global incidence and mortality. Mutated genes or dysregulated pathways responsible for CRC progression have been identified and employed as biomarkers for diagnosis and prognosis. In this study, a ubiquitination regulator, MARCH9, was shown to accelerate CRC progression both <italic>in vitro</italic> and <italic>in vivo</italic>. CRC samples from The Cancer Genome Atlas (TCGA) showed significantly upregulated MARCH9 expression by individual cancer stage, histological subtype, and nodal metastasis status. Knockdown of <italic>MARCH9</italic> inhibited, while <italic>MARCH9</italic> overexpression promoted, CRC cell proliferation and migration. Knockdown of <italic>MARCH9</italic> also induced CRC cell apoptosis and caused cell cycle arrest. Further investigation showed that MARCH9 promoted CRC progression by downregulating the expression of a deubiquitinase cylindromatosis (<italic>CYLD</italic>) gene and activating p65, a member of the nuclear factor-κB (NF-κB) protein family. Finally, <italic>in vivo</italic> xenograft studies confirmed that <italic>MARCH9</italic> knockdown suppressed tumor growth in nude mice. Thus, this study demonstrated that MARCH9 may be a novel and effective therapeutic target for CRC therapy.</p>