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

Targeting MALT1 Suppresses the Malignant Progression of Colorectal Cancer via miR-375/miR-365a-3p/NF-κB Axis.
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靶向MALT 1通过miR-375/miR-365 a-3 p/NF-κB轴抑制结直肠癌恶性进展

DOI:
10.3389/fcell.2022.845048
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发表时间:
2022
影响因子:
5.5
通讯作者:
Deng H
Deng H
中科院分区:
生物学2区
文献类型:
--
作者:
Qian R;Niu X;Wang Y;Guo Z;Deng X;Ding Z;Zhou M;Deng H

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结直肠癌(Colorectal cancer,CRC)是世界上发病率第二高、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。在这里,粘膜相关淋巴组织淋巴瘤易位蛋白1(MALT 1),被称为NF-κB信号通路的上游,被鉴定为在CRC肿瘤和细胞系中高度上调。此外,通过MI-2下调MALT 1或抑制其蛋白水解功能抑制CRC细胞的细胞增殖和迁移。在体内,抑制MALT 1表达或其蛋白酶体活性有效地减少了裸鼠皮下肿瘤的大小。在机制上,miR-375和miR-365 a-3 p被鉴定为通过靶向MALT 1抑制NF-κB活化。总之,我们的研究结果强调了一个新的调节轴,miRNA-MALT 1-NF-κB,在CRC的进展中起着至关重要的作用,并为临床治疗提供了新的和有希望的治疗靶点。
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. In vivo, 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 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 provides novel and hopeful therapeutic targets for clinical treatment.
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