AP3M2:神经系统的一个关键调节因子调节结直肠癌的自噬作用

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-10-31 DOI:10.1016/j.tice.2024.102593
Maguie El Boustani , Nayla Mouawad , Monah Abou Alezz
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引用次数: 0

摘要

结直肠癌(CRC)每年影响约一百万人,死亡率高达 50%,占全球癌症相关死亡人数的 8%。通过癌症基因组图谱(The Cancer Genome Atlas)对这些肿瘤亚型进行分子特征描述有助于发现 "可用药 "基因。我们的研究通过采用 RNA 干扰使 AP3M2 失活,重点研究了 AP3M2 基因(适配器相关蛋白复合物 3 亚基μ2)作为潜在癌基因的意义。AP3M2 在神经细胞中参与蛋白质向溶酶体和特化细胞器的转运,在 CRC 细胞系中被扩增。敲除 AP3M2 能显著降低 HCT-116、CACO2 和 HT29 三种 CRC 细胞系的存活率。耐人寻味的是,我们的研究结果表明,在 CRC 细胞系中,AP3M2 的表达与自噬相关基因以及活性氧(ROS)水平之间存在相互作用。这些结果表明,靶向 AP3M2 可以通过自噬-ROS 机制为治疗 CRC 提供一种强有力的策略。
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AP3M2: A key regulator from the nervous system modulates autophagy in colorectal cancer
Colorectal cancer (CRC) affects approximately a million people annually with a mortality rate of 50 %, accounting for 8 % of cancer-related deaths globally. Molecular characterization by The Cancer Genome Atlas could be useful in these tumor subtypes to reveal "druggable" genes. Our study focuses on the significance of the AP3M2 gene (adaptor-related protein complex 3 subunit mu 2) as a potential oncogene by employing RNA interference to inactivate AP3M2. AP3M2, inplicated in protein trafficking to lysosomes pathway and specialized organelles in neuronal cells, was amplified in CRC cell lines. The Knockdown of AP3M2 significantly reduced the viability of three CRC cell lines HCT-116, CACO2, and HT29. Intriguingly, our findings revealed an interaction between AP3M2 expression and autophagy-related genes, as well as reactive oxygen species (ROS) levels in CRC cell lines. These results suggest that targeting AP3M2 could provide a powerful strategy for CRC treatment through autophagy-ROS mechanism.
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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