环状RNA001380通过miR-30b诱导KRAS野生型结直肠癌患者西妥昔耐药的机制研究

前期研究发现miR-30b通过与KRAS结合可以抑制结直肠癌细胞的增殖能力，预实验提示circ-001380与miR-30b可结合，组织标本中circ-001380的表达与miR-30b表达趋势相反，与KRAS表达趋势一致；为了证实circ-001380通过miR-30b诱导KRAS野生型细胞西妥昔耐药，我们将在EGFR阳性且KRAS野生型的细胞中构建模型，结合分子、细胞及动物原位移植模型研究circ-001380及miR-30b的作用机制及二者对细胞功能的影响，对KRAS基因表达的影响、对KRAS下游信号通路的影响以及对结直肠癌细胞西妥昔耐药的影响；为结直肠癌KRAS野生型患者西妥耐药寻找有效的分子标志物及治疗靶标。

Previous studies showed that miR-30b could inhibit the proliferation of colorectal cancer cells by combining with KRAS. Pre-experiment suggested that circ-001380 could bind to miR-30b. The expression of circ-001380 in tissue samples was opposite to that of miR-30b.While the expression of circ001380 is consistent with KRAS’s expression. In order to demonstrate that circ-001380 could induce wild-type KRAS patients cetuximab-resistant by targeting miR-30b.We further constructed cell models in EGFR-positive and wild-type KRAS colorectal cancer cell lines. The mechanism of circ-001380 and miR-30b was studied by molecular experiments, cell experiments and visualization of colon cancer in situ transplantation in EGFR-positive and wild-type KRAS colorectal cancer cell lines. Meanwhile, we will detect the expression of KRAS, the KRAS signal pathway and the Cetuxine resistance on colon cancer cells. We will explore the mechanism of Cetuxine resistance on wild-type KRAS colorectal cancer cells by circ-001380 and miR-30b. Finally find the effective molecular marker for wild-type KRAS CRC patients with cetirizine resistance.