Center for Laboratory Medicine, the Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou 412000, China.
Changsha KingMed Center for Clinical Laboratory Co., Ltd, Changsha 410006, China.
Exp Mol Pathol. 2021 Jun;120:104635. doi: 10.1016/j.yexmp.2021.104635. Epub 2021 Mar 25.
MicroRNA (miR)-93 has been proven to mediate the initiation and progression of colorectal carcinoma (CRC); however, the mechanisms by which miR-93 mediates CRC development need deeper elucidation. The present study is designed to investigate the association between miR-93 and high mobility group box 3 (HMGB3), as well as the functions of miR-93, in CRC.
miR-93 expression was quantified by RT-qPCR. CRC cells were transfected or cotransfected with miR-93 mimic, miR-93 inhibitor, pcDNA3.1-HMGB3 and sh-HMGB3, and then the proliferative, migratory and invasive capacities were detected in addition to the apoptotic rate. Western blotting assessed the expression levels of HMGB3, PI3K, p-PI3K, AKT and p-AKT. The interaction between miR-93 and HMGB3 was identified.
In CRC tissues, miR-93 was downregulated and HMGB3 was upregulated. LOVO and SW480 cells transfected with miR-93 mimic exhibited reduced proliferation, invasion and migration as well as increased apoptosis. The ratios of p-PI3K/PI3K and p-AKT/AKT were declined after miR-93 mimic was introduced into the CRC cell lines. miR-93 negatively downregulated HMGB3, and introduction of pcDNA3,1-HMGB3 could counteract, in part, the inhibitory effects of miR-93 on the malignant properties of CRC cells as well as the ratios of p-PI3K/PI3K and p-AKT/AKT.
miR-93 targeted HMGB3 to block the activation of the PI3K/AKT pathway and thus enhance CRC cell apoptosis.
微小 RNA（miR）-93 已被证明介导结直肠癌（CRC）的发生和发展；然而，miR-93 介导 CRC 发展的机制需要更深入的阐明。本研究旨在探讨 miR-93 与高迁移率族蛋白 B3（HMGB3）之间的关联，以及 miR-93 在 CRC 中的功能。
通过 RT-qPCR 定量 miR-93 的表达。CRC 细胞转染或共转染 miR-93 模拟物、miR-93 抑制剂、pcDNA3.1-HMGB3 和 sh-HMGB3，然后检测增殖、迁移和侵袭能力以及细胞凋亡率。Western blot 检测 HMGB3、PI3K、p-PI3K、AKT 和 p-AKT 的表达水平。鉴定 miR-93 和 HMGB3 之间的相互作用。
在 CRC 组织中，miR-93 下调，HMGB3 上调。转染 miR-93 模拟物的 LOVO 和 SW480 细胞增殖、侵袭和迁移能力降低，凋亡增加。将 miR-93 模拟物引入 CRC 细胞系后，p-PI3K/PI3K 和 p-AKT/AKT 的比值下降。miR-93 负下调 HMGB3，转染 pcDNA3.1-HMGB3 部分逆转了 miR-93 对 CRC 细胞恶性特性以及 p-PI3K/PI3K 和 p-AKT/AKT 比值的抑制作用。
miR-93 靶向 HMGB3 阻断 PI3K/AKT 通路的激活，从而增强 CRC 细胞凋亡。
