Department of Orthopaedics, Huishan District People's Hospital, Wuxi, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2218-2228. doi: 10.26355/eurrev_202003_20487.
Osteosarcoma (OS) is a frequent bone malignancy. Long non-coding RNA myocardial infarction associated transcript (MIAT) has been reported to be involved in the development of human cancers, including OS. However, the mechanism underlying MIAT in OS progression remains largely unclear.
The expression levels of MIAT and sineoculis homeobox homolog 1 (SIX1) in OS tissues and cells were detected by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, migration and invasion of OS cells were determined by MTT, flow cytometry and trans-well assays, respectively. The target interaction among MIAT, miR-141-3p and SIX1 was analyzed by bioinformatics analysis and luciferase reporter assay. Phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway was evaluated by Western blot.
MIAT and SIX1 expression levels were enhanced in OS tissues and cells. Knockdown of MIAT or SIX1 repressed cell viability, migration and invasion but promoted apoptosis in OS cells. Moreover, overexpression of SIX1 reversed the inhibitive role of MIAT silence in OS progression. Furthermore, MIAT could increase SIX1 expression by competitively sponging miR-141-3p. Besides, inhibition of MIAT blocked PI3K/AKT pathway by decreasing SIX1 in OS cells.
MIAT silence suppresses OS progression through inactivating PI3K/AKT signaling by sponging miR-141-3p to regulate SIX1, indicating a novel target for the treatment of OS.
骨肉瘤（OS）是一种常见的骨恶性肿瘤。长链非编码 RNA 心肌梗塞相关转录物（MIAT）已被报道参与人类癌症的发展，包括 OS。然而，MIAT 在 OS 进展中的作用机制在很大程度上仍不清楚。
通过定量实时聚合酶链反应和 Western blot 检测 OS 组织和细胞中 MIAT 和 sineoculis 同源盒同源物 1（SIX1）的表达水平。通过 MTT、流式细胞术和 Transwell 测定分别测定 OS 细胞的活力、凋亡、迁移和侵袭。通过生物信息学分析和荧光素酶报告基因测定分析 MIAT、miR-141-3p 和 SIX1 之间的靶相互作用。通过 Western blot 评估磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路。
MIAT 和 SIX1 的表达水平在 OS 组织和细胞中升高。沉默 MIAT 或 SIX1 抑制 OS 细胞的活力、迁移和侵袭，但促进细胞凋亡。此外，过表达 SIX1 逆转了 MIAT 沉默对 OS 进展的抑制作用。此外，MIAT 可以通过竞争性海绵吸附 miR-141-3p 增加 SIX1 的表达。此外，在 OS 细胞中抑制 MIAT 通过降低 SIX1 来阻断 PI3K/AKT 通路。
沉默 MIAT 通过海绵吸附 miR-141-3p 来调节 SIX1，从而抑制 PI3K/AKT 信号通路，抑制 OS 进展，为 OS 的治疗提供了一个新的靶点。
