PDF(Pubmed)
Abstract：
Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According to reports, the development of CRC is linked to miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between CRC tissues and adjacent tissues. However, it is unclear whether there is a correlation between miR-135b-5p and cetuximab (CTx) resistance in CRC. Use the GEO database to measure miR-135b-5p expression in CRC. Additionally, RT-qPCR was applied to ascertain the production level of miR-135b-5p in three human CRC cells and NCM460 cells. The capacity of cells to migrate and invade was examined utilizing the wound-healing and transwell assays, while the CCK-8 assay served for evaluating cell viability, as well as colony formation assays for proliferation. The expected target protein of miR-135b-5p in CRC cell cetuximab resistance has been investigated using western blot. Suppression of miR-135b-5p could increase the CTx sensitivity of CTx-resistant CRC cells, as manifested by the attenuation of proliferation, migration, and invasion ability. Mechanistic studies revealed miR-135b-5p regulates the epithelial-to-mesenchymal transition (EMT) process and Wnt/β-catenin signaling pathway through downgulating FOXN3. In short, knockdowning miR-135b-5p could increase FOXN3 expression in CRC cells, promote the EMT process, and simultaneously activate the Wnt/β-catenin signaling pathway to elevate CTx resistance in CRC cells.
摘要：
尽管靶向治疗取得了进展，原发性和获得性耐药性使结直肠癌（CRC）的治疗成为亟待解决的问题。据报道,CRC的发展与miRNA失调有关。多项研究已经证明miR-135b-5p在CRC组织和邻近组织之间具有异常表达水平。然而,目前尚不清楚miR-135b-5p与CRC中西妥昔单抗(CTx)耐药是否存在相关性.使用GEO数据库测量miR-135b-5p在CRC中的表达。此外,应用RT-qPCR来确定miR-135b-5p在三种人CRC细胞和NCM460细胞中的产生水平。利用伤口愈合和transwell测定法检查细胞迁移和侵入的能力，虽然CCK-8测定用于评估细胞活力，以及增殖的集落形成测定。已经使用蛋白质印迹研究了CRC细胞西妥昔单抗抗性中miR-135b-5p的预期靶蛋白。抑制miR-135b-5p可提高CTx耐药CRC细胞的CTx敏感性,如增殖减弱所示，迁移,和入侵能力。机制研究显示miR-135b-5p通过下调FOXN3调节上皮-间质转化(EMT)过程和Wnt/β-catenin信号通路。总之,敲除miR-135b-5p可以增加CRC细胞中FOXN3的表达，推进EMT流程，同时激活Wnt/β-catenin信号通路提高CRC细胞的CTx抗性。
