Wang Haoyu, Ma Yurui, Lin Yifan, Chen Rui, Xu Bin, Deng Jiali
Department of Chemistry, Qianweichang College, Shanghai University, Shanghai, China.
School of Life Science, Shanghai University, Shanghai, China.
Front Genet. 2020 Jan 10;10:1320. doi: 10.3389/fgene.2019.01320. eCollection 2019.
Colorectal cancer is one of the most leading causes of death. Searching for new therapeutic targets for colorectal cancer is urgently needed. SHU00238, an isoxazole derivative, was reported to suppress colorectal tumor growth through microRNAs. But the underlying mechanisms still remain unknown. Here, we explored the mechanism of SHU00238 on colorectal cancer by RT-PCR, CCK-8, flow cytometry, mirTarBase, and GO enrichment analysis. We screened partial microRNAs regulated by SHU00238 in colorectal cancer cells. Furthermore, we identified that miR-4701-3p and miR-4793-3p can reverse the acceleration of SHU00238 on colorectal cancer cell apoptosis in HCT116 Cells. Finally, we found that SMARCA5, MBD3, VPS53, EHD4 are estimated to mediate the regulation of miR-4701-3p and miR-4793-3p on colorectal cancer cell apoptosis, which targets ATP-dependent chromatin remodeling pathway and endocytic recycling pathway. Taken together, our study reveals that SHU00238 promotes colorectal cancer cell apoptosis through miR-4701-3p and miR-4793-3p, which provide a potential drug target and therapeutic strategy for colorectal cancer.
结直肠癌是主要的死亡原因之一。迫切需要寻找结直肠癌的新治疗靶点。异恶唑衍生物SHU00238据报道可通过微小RNA抑制结直肠癌肿瘤生长。但其潜在机制仍不清楚。在此,我们通过逆转录聚合酶链反应、细胞计数试剂盒-8、流式细胞术、miRTarBase和基因本体富集分析探索了SHU00238对结直肠癌的作用机制。我们筛选了SHU00238在结直肠癌细胞中调控的部分微小RNA。此外,我们确定miR-4701-3p和miR-4793-3p可逆转SHU00238对HCT116细胞中结直肠癌细胞凋亡的促进作用。最后,我们发现SMARCA5、MBD3、VPS53、EHD4估计介导miR-4701-3p和miR-4793-3p对结直肠癌细胞凋亡的调控,其靶向ATP依赖的染色质重塑途径和内吞再循环途径。综上所述,我们的研究表明SHU00238通过miR-4701-3p和miR-4793-3p促进结直肠癌细胞凋亡,这为结直肠癌提供了一个潜在的药物靶点和治疗策略。