Qian Rui, Niu Xinli, Wang Yinghui, Guo Zhi, Deng Xuyi, Ding Zhenhua, Zhou Meijuan, Deng Haijun
Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
Front Cell Dev Biol. 2022 Mar 2;10:845048. doi: 10.3389/fcell.2022.845048. eCollection 2022.
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 the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. , suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation 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 provides novel and hopeful therapeutic targets for clinical treatment.
结直肠癌（CRC）是全球发病率第二高、死亡率第三高的恶性肿瘤，而靶向药物的治疗选择仍然有限。在此，被认为是核因子κB信号通路上游分子的黏膜相关淋巴组织淋巴瘤易位蛋白1（MALT1），被发现在CRC肿瘤和细胞系中高度上调。此外，MALT1的下调或MI-2对其蛋白水解功能的抑制，抑制了CRC细胞的增殖和迁移。抑制MALT1表达或其蛋白酶体活性有效减小了裸鼠皮下肿瘤的大小。机制上，已确定miR-375和miR-365a-3p通过靶向MALT1抑制核因子κB激活。总体而言，我们的结果表明，一个新的调控轴miRNA-MALT1-核因子κB在CRC进展中起关键作用，并为临床治疗提供了新的、有希望的治疗靶点。
