miR-421 载体壳聚糖纳米粒子抑制结直肠癌细胞的恶性特征

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-03-01 DOI:10.1166/jbn.2024.3790

Yunxiao Li, Bin Zhou, Jiayu Zhang, Yuenan Yang, Qianqian Cui

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引用次数: 0

摘要

直肠癌（RC）是一种破坏性癌症，长期化疗往往会导致药物敏感性降低。本研究探讨了携带miR-421的壳聚糖纳米颗粒（NPs）在RC中的作用及其通过Wnt/β-catenin信号通路抑制RC细胞恶性特征的机制。制备了载miR-421的壳聚糖NPs，然后将HR8348细胞分为模型组、对照组、壳聚糖NPs组（纳米组）、miR-421组和携带miR-421的壳聚糖NPs组（纳米+miR-421组）、Wnt1过表达组（pc-Wnt1组）、Wnt1抑制组（si-Wnt1组）和纳米+miR-421+si-Wnt1组，细胞分别接受相应的处理。处理后，检测了 RC 细胞中 Wnt1/β-catenin 和 c-Myc 的表达，并确定了 miR-421 的靶基因。实验还对 RC 细胞的恶性生物学行为进行了评估。携带 miR-421 的壳聚糖 NPs 显著抑制了 RC 细胞的迁移和增殖，并促进了细胞凋亡。miR-421的出现抑制了Wnt1/β-catenin表达的增加，而Wnt1抑制剂则控制了RC细胞的特性，携带miR-421的壳聚糖NPs的抑制作用最为突出。生物信息学软件 RegRNA 2.0 预测 Wnt1/β-catenin 是受 miR-421 调控的特异性靶基因。通过阻断Wnt1/β-catenin信号通路和下调c-Myc的表达，负载了miR-421的壳聚糖NPs能有效抑制RC细胞的生长。

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

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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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.