AUTHOR=Qian Rui , Niu Xinli , Wang Yinghui , Guo Zhi , Deng Xuyi , Ding Zhenhua , Zhou Meijuan , Deng Haijun 

TITLE=Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.845048

DOI=10.3389/fcell.2022.845048

ISSN=2296-634X

ABSTRACT=Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as upstream of NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed cell proliferation and migration of CRC cells. In vivo, suppressing MALT1 expression or its proteasome activity effectively reduced the size of subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibited NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis miRNA-MALT1-NF-κB plays a vital role in the progression of CRC and provide novel and hopeful therapeutic targets for clinical treatment.