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

Abstract

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.