Department of Oncology, Jiangxi Chest Hospital, Nanchang, Jiangxi, P.R. China.
J Biol Regul Homeost Agents. 2021 Mar-Apr;35(2):473-484. doi: 10.23812/20-570-A.
Exosomes are involved in a range of processes in lung cancer such as cell proliferation, metastasis, and angiogenesis. Tumor-derived exosomes participate in the formation and progression of lung cancer by delivering functional biomolecules, including microRNAs (miRNA). The purpose of the present study was to determine the role of lung cancer cell-derived exosomal miR-210 in the proliferation and invasion of lung cancer cells and its underlying mechanism. Initially, exosomes were isolated from A549 cells and characterized by transmission electron microscopy and assessment of exosomal marker expression. RT-qPCR determined that miR-210 expression was elevated in exosomes as well as lung cancer cells. As reflected by dual-luciferase reporter assay, miR-210 negatively regulated RUNX3 expression. Following loss- and gain- function assay, it was found that miR-210 inhibition suppressed biological properties of A549 and H460 cells, which could be reversed by the silencing of RUNX3. miR-210 elevation induced the p-PI3K/PI3K and p-AKT/AKT levels, suggesting the activation of PI3K/AKT signaling pathway. Collectively, exosomal miR-210 targeted and negatively regulated RUNX3 expression to promote malignant properties of lung cancer cells by potentiating PI3K/AKT signaling pathway.
外泌体参与肺癌的多种过程，如细胞增殖、转移和血管生成。肿瘤来源的外泌体通过传递包括 microRNA（miRNA）在内的功能性生物分子参与肺癌的形成和进展。本研究旨在确定肺癌细胞来源的外泌体 miR-210 在肺癌细胞增殖和侵袭中的作用及其潜在机制。首先，通过透射电子显微镜和外泌体标志物表达评估分离 A549 细胞来源的外泌体并进行鉴定。RT-qPCR 确定 miR-210 在肺癌细胞和外泌体中表达上调。双荧光素酶报告基因检测表明，miR-210 负调控 RUNX3 表达。通过缺失和获得功能实验发现，miR-210 抑制可抑制 A549 和 H460 细胞的生物学特性，而 RUNX3 的沉默可逆转这种抑制作用。miR-210 上调诱导 p-PI3K/PI3K 和 p-AKT/AKT 水平，提示 PI3K/AKT 信号通路被激活。综上所述，外泌体 miR-210 通过增强 PI3K/AKT 信号通路靶向并负调控 RUNX3 表达，从而促进肺癌细胞的恶性特性。
