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长链非编码 RNA MALAT1 通过靶向 miR-873-5p/ROCK1 调节骨肉瘤细胞的增殖、凋亡、迁移和侵袭。

IncRNA MALAT1 Regulates the Proliferation, Apoptosis, Migration, and Invasion of Osteosarcoma Cells by Targeting miR-873-5p/ROCK1.

机构信息

Department of Bone and Soft-Tissue Tumor, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, Shanxi, China.

出版信息

Crit Rev Eukaryot Gene Expr. 2023;33(2):67-79. doi: 10.1615/CritRevEukaryotGeneExpr.2022044747.

Abstract

The malignant bone tumor osteosarcoma (OS) was one of the most aggressive tumors. Despite breakthroughs in treatment options for OS recently, the survival rate of patients with metastasis or reoccurring disease has remained unchanged over the last 25 years, at around 20%. lncRNA expression dysregulation is linked to carcinogenesis, advancement, and metastasis. Additionally, the fundamental mechanism of lncRNAs in regulating OS cell biological activity and progression is still being investigated. The expression of miR-873-5p and MALAT1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS. The relationship between the expression level of MALAT1 and the survival rate of OS individuals was evaluated by the Kaplan-Meier plotter. The tumor cell's capability of proliferation was determined using the CCK-8. Transwell was used to test the migratory and invasive properties of tumor cells. ROCK1 protein expression was analyzed by western blot, while qRT-PCR was used to detect ROCK1 mRNA expression. Targeted genes of MALAT1 or miR-873-5p were predicted by StarBase2.0. The target association among miR-873-5p and MALAT1 or ROCK1 was confirmed using the luciferase assay. The relationship between ROCK1 and MALAT1 or miR-873-5p expression in OS was investigated using Spearman's correlation analysis. MALAT1 was up-regulated and was linked to a lower survival rate of patients in OS. The malignant behaviors of cells were inhibited by down-regulated MALAT1 in vitro. Dual-luciferase gene experiments confirmed the presence of MALAT1/miR-873-5p/ROCK1 axis. The up-regulated miR-873-5p blocked the promoted effects of MALAT1 on cell behaviors. Over-expressed MALAT1 promoted the malignant behaviors of cells by miR-873-5p/ROCK1 axis in OS.

摘要

恶性骨肿瘤骨肉瘤(OS)是最具侵袭性的肿瘤之一。尽管最近在 OS 的治疗选择方面取得了突破,但转移性或复发性疾病患者的生存率在过去 25 年中仍保持不变,约为 20%。lncRNA 表达失调与癌症发生、进展和转移有关。此外,lncRNAs 调节 OS 细胞生物学活性和进展的基本机制仍在研究中。通过实时定量聚合酶链反应(qRT-PCR)检测 OS 中 miR-873-5p 和 MALAT1 的表达。通过 Kaplan-Meier 绘图器评估 MALAT1 的表达水平与 OS 个体生存率之间的关系。通过 CCK-8 测定肿瘤细胞的增殖能力。使用 Transwell 测试肿瘤细胞的迁移和侵袭特性。通过 Western blot 分析 ROCK1 蛋白表达,通过 qRT-PCR 检测 ROCK1 mRNA 表达。通过 StarBase2.0 预测 MALAT1 或 miR-873-5p 的靶向基因。使用荧光素酶测定法证实 miR-873-5p 和 MALAT1 或 ROCK1 之间的靶基因关联。使用 Spearman 相关分析研究 OS 中 ROCK1 与 MALAT1 或 miR-873-5p 表达之间的关系。MALAT1 上调与 OS 患者生存率降低有关。在体外下调 MALAT1 可抑制细胞的恶性行为。双荧光素酶基因实验证实了 MALAT1/miR-873-5p/ROCK1 轴的存在。上调的 miR-873-5p 阻断了 MALAT1 对细胞行为的促进作用。过表达的 MALAT1 通过 miR-873-5p/ROCK1 轴促进 OS 细胞的恶性行为。

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