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长链非编码 RNA ADPGK-AS1 通过靶向 miR-542-3p 调控骨肉瘤细胞的增殖、侵袭、迁移和凋亡。

LncRNA ADPGK-AS1 regulated cell proliferation, invasion, migration and apoptosis via targeting miR-542-3p in osteosarcoma.

机构信息

Department of Orthopedics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8751-8760. doi: 10.26355/eurrev_201910_19269.

Abstract

OBJECTIVE

The functions of lncRNAs have been verified to be important biomarkers and regulators for diagnosis and treatment of human diseases. In osteosarcoma (OS), emerging evidence determined that lncRNA was associated with cell progression. However, due to the high incidence and recurrence rate of osteosarcoma, it is important to find an effective treatment for osteosarcoma.

PATIENTS AND METHODS

QRT-PCR was used to detect the expression of ADPGK-AS1 and miR-542-3p in tissues and cells. Western blot was applied to measure the protein expression of CDK4, Cyclin D1, Bcl-2, Bax, Cleaved caspase-3, MMP-2, and MMP-9. MTT assay and flow cytometry were used to measure cell proliferation and apoptosis. Cell invasion and migration were determined using the transwell assay. Moreover, luciferase reporter assay was used to ensure the relation between ADPGK-AS1 and miR-542-3p.

RESULTS

LncRNA ADPGK-AS1 expression was induced while miR-542-3p expression was reduced in OS tissues and cells. Functional experiments showed that inhibition of ADPGK-AS1 could decrease cell proliferation, migration, and invasion, as well as promoted cell apoptosis in OS cells. Also, miR-542-3p has been verified to be a target miRNA of ADPGK-AS1 and miR-542-3p could reverse the effects of ADPGK-AS1 on cell proliferation, apoptosis, migration, and invasion in OS cells.

CONCLUSIONS

ADPGK-AS1 affected cell proliferation, invasion, migration, and apoptosis via targeting miR-542-3p in OS, providing a theoretical basis and a new therapeutic target for the diagnosis and treatment of OS.

摘要

目的

长链非编码 RNA(lncRNA)的功能已被证实是人类疾病诊断和治疗的重要生物标志物和调节剂。在骨肉瘤(OS)中,新出现的证据表明 lncRNA 与细胞进展有关。然而,由于骨肉瘤的发病率和复发率较高,因此寻找有效的骨肉瘤治疗方法非常重要。

患者和方法

使用 QRT-PCR 检测组织和细胞中 ADPGK-AS1 和 miR-542-3p 的表达。Western blot 用于测量 CDK4、Cyclin D1、Bcl-2、Bax、Cleaved caspase-3、MMP-2 和 MMP-9 的蛋白表达。MTT assay 和流式细胞术用于测量细胞增殖和凋亡。使用 Transwell assay 测定细胞侵袭和迁移。此外,还使用荧光素酶报告基因 assay 来确定 ADPGK-AS1 与 miR-542-3p 之间的关系。

结果

在 OS 组织和细胞中,lncRNA ADPGK-AS1 的表达增加,而 miR-542-3p 的表达减少。功能实验表明,抑制 ADPGK-AS1 可降低 OS 细胞的增殖、迁移和侵袭,并促进细胞凋亡。此外,已经验证 miR-542-3p 是 ADPGK-AS1 的靶 miRNA,miR-542-3p 可以逆转 ADPGK-AS1 对 OS 细胞增殖、凋亡、迁移和侵袭的影响。

结论

ADPGK-AS1 通过靶向 OS 中的 miR-542-3p 影响细胞增殖、侵袭、迁移和凋亡,为 OS 的诊断和治疗提供了理论依据和新的治疗靶点。

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