■耐药性是乳腺癌治疗的主要障碍。已报道环状RNA(circircRNA)circ-MMP11促进乳腺癌的进展。本研究旨在探讨circ-MMP11在乳腺癌拉帕替尼耐药中的作用及机制。
■Circ-MMP11,microRNA-153-3p(miR-153-3p),通过实时定量聚合酶链反应(RT-qPCR)检测Anillin(ANLN)水平。细胞活力,殖民地的数量,凋亡,迁移,并通过3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-溴化四唑(MTT)检测到侵袭,菌落形成,流式细胞术,和transwell分析,分别。施加外泌体并通过差速离心和透射电子显微镜检测。通过蛋白质印迹测定评估CD63、CD9和ANLN的蛋白质水平。miR-153-3p与circ-MMP11或ANLN之间的结合关系通过circirinteractome或starbase预测,然后通过双荧光素酶报告基因测定和RNA下拉测定进行验证。通过体内移植瘤模型检测circ-MMP11对乳腺癌肿瘤生长和耐药的生物学作用。
■Circ-MMP11和ANLN高表达,miR-153-3p在LR乳腺癌组织和细胞中降低。Circ-MMP11可以通过外泌体运输。此外,Circ-MMP11敲低通过抑制细胞活力促进拉帕替尼敏感性,菌落数,迁移,入侵,并促进LR乳腺癌细胞的凋亡。Circ-MMP11缺乏提高了体内乳腺癌的药物敏感性。机械上,circ-MMP11可以通过构建miR-153-3p来调节ANLN的表达。
■Circ-MMP11可以通过外泌体转移到乳腺癌细胞中。circ-MMP11作为miR-153-3p的海绵调节ANLN的表达,从而促进乳腺癌细胞的拉帕替尼耐药性,为乳腺癌的治疗提供治疗靶点。
UNASSIGNED: Drug-resistance is a major obstacle to the treatment of breast cancer. Circular RNA (circRNA) circ-MMP11 has been reported to be promoting the progression of breast cancer. This study is designed to explore the role and mechanism of circ-MMP11 in lapatinib resistance in breast cancer.
UNASSIGNED: Circ-MMP11, microRNA-153-3p (miR-153-3p), and Anillin (
ANLN) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, number of colonies, apoptosis, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, flow cytometry, and transwell assays, respectively. Exosomes were exerted and detected by differential centrifugation and a transmission electron microscope. The protein levels of CD63, CD9, and
ANLN were assessed by western blot assay. The binding relationship between miR-153-3p and circ-MMP11 or
ANLN was predicted by circinteractome or starbase, and then verified by a dual-luciferase reporter assay and RNA pull-down assay. The biological role of circ-MMP11 on breast cancer tumor growth and drug resistance was detected by the xenograft tumor model in vivo.
UNASSIGNED: Circ-MMP11 and
ANLN were highly expressed, and miR-153-3p was decreased in LR breast cancer tissues and cells. Circ-MMP11 could be transported by exosomes. Furthermore, circ-MMP11 knockdown promoted lapatinib sensitivity by repressing cell viability, colony number, migration, invasion, and boosting apoptosis in LR breast cancer cells. Circ-MMP11 deficiency improved the drug sensitivity of breast cancer in vivo. Mechanically, circ-MMP11 could regulate
ANLN expression through sponging miR-153-3p.
UNASSIGNED: Circ-MMP11 could be transferred by exosomes in breast cancer cells. And circ-MMP11 functioned as a sponge of miR-153-3p to regulate ANLN expression, thereby promoting lapatinib resistance in breast cancer cells, providing therapeutic targets for the treatment of breast cancer.