Abstract
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.
Highlights
Colorectal cancer (CRC) is one of the most common malignant tumors that endanger human health
We identified that miR-4701-3p and miR-4793-3p can reverse the acceleration of SHU00238 on CRC cell apoptosis in HCT116 Cells by CCK-8 and flow cytometry
Our study reveals that SHU00238 promotes CRC cell apoptosis through miR-4701-3p and miR-4793-3p, which provide a potential drug target and therapeutic strategy for CRC
Summary
Colorectal cancer (CRC) is one of the most common malignant tumors that endanger human health. According to the latest statistics, the incidence of CRC ranks third among malignant tumors worldwide and the mortality rate ranks second. The treatment of CRC mainly uses surgery, radiotherapy, chemotherapy, exercises, and chemical synthetic antineoplastic drugs (Nilsson et al, 2013; Kuipers et al, 2015; Mach and Fuster-Botella, 2017; Batacan et al, 2018). Most of the patients had been diagnosed in the middle and late stages and were insensitive to radiotherapy (Hosseinimehr et al, 2019), and new antineoplastic drugs are expensive and have some side effects (Baker et al, 2000).
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