miR-421-Loaded Chitosan Nanoparticles Suppress the Malignant Characteristics of Colorectal Cancer Cells

壳聚糖 Wnt信号通路 细胞凋亡 结直肠癌 化学 癌细胞 癌症研究 连环素 信号转导 癌症 生物 医学 生物化学 内科学
作者
Yunxiao Li,Bin Zhou,Jiayu Zhang,Yuenan Yang,Qianqian Cui
出处
期刊:Journal of Biomedical Nanotechnology [American Scientific Publishers]
卷期号:20 (3): 467-474
标识
DOI:10.1166/jbn.2024.3790
摘要

Rectal cancer (RC) is a destructive cancer and long-term chemotherapy often leads to decreased drug sensitivity. This study investigates the role of chitosan nanoparticles (NPs) carrying miR-421 in RC and the mechanism underlying its inhibitory effect on malignant characteristics of RC cells through Wnt/ β -catenin signaling pathway. miR-421-loaded chitosan NPs were prepared, and then HR8348 cells were divided into model group, control group, chitosan NPs group (nano-group), miR-421 group and chitosan NPs carrying miR-421 group (nano+miR-421 group), Wnt1 overexpression group (pc-Wnt1 group), Wnt1 inhibition group (si-Wnt1 group), and nano+miR-421+si-Wnt1 group, in which the cells received corresponding treatment. After treatment,Wnt1/ β -catenin and c-Myc expression in RC cells was detected and the target gene of miR-421 was identified. Various experiments were conducted to assess the malignant biological behavior of RC cells. Chitosan NPs carrying miR-421 significantly suppressed migration and proliferation of RC cells and promoted apoptosis. The advent of miR-421 inhibited the increase of Wnt1/ β -catenin expression, while Wnt1 inhibitor, as such, controlled characteristics of RC cells, and the inhibitory role of chitosan NPs carrying miR-421 was the most prominent. The bioinformatics software RegRNA 2.0 predicted Wnt1/ β -catenin as the specific target gene regulated by miR-421. Chitosan NPs loaded with miR-421 effectively inhibit RC cell growth through blocking the Wnt1/ β -catenin signaling pathway and down-regulating the expression of c-Myc.

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