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长链非编码RNA ASB16-AS1作为miR-760的海绵,通过增加HDGF表达促进骨肉瘤的恶性表型。

Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression.

作者信息

Yin Ruofeng, Liu Junzhi, Zhao Dongxu, Wang Fei

机构信息

Department of Orthopedics, China-Japan Union Hospital Jilin University, Changchun, Jilin 130033, People's Republic of China.

Department of Quality Control, China-Japan Union Hospital Jilin University, Changchun, Jilin 130033, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Mar 13;13:2261-2274. doi: 10.2147/OTT.S240022. eCollection 2020.

DOI:10.2147/OTT.S240022
PMID:32214826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7081065/
Abstract

PURPOSE

ASB16 antisense RNA 1 (ASB16-AS1) is a cancer-associated long non-coding RNA that contributes to tumorigenesis and tumor development. Nevertheless, to the best of our knowledge, whether and how ASB16-AS1 is implicated in osteosarcoma (OS) malignancy remains unclear and therefore warrants exploration. Our current study focused on making in-depth investigation of ASB16-AS1 in OS. In the present study, the expression pattern of ASB16-AS1 in OS tissues and cell lines was analyzed. In addition, we examined the clinical value of ASB16-AS1 for OS patients. Furthermore, we explored the impacts of ASB16-AS1 on the malignant phenotype of OS cells in vitro and in vivo as well as the underlying mechanism.

METHODS

ASB16-AS1, microRNA-760 (miR-760) and hepatoma-derived growth factor (HDGF) expressions were measured using reverse transcription-quantitative PCR. Cell proliferation and apoptosis were evaluated using CCK-8 and flow cytometry analyses, respectively, and cell migration and invasion were determined via cell migration and invasion assays.

RESULTS

ASB16-AS1 expression was significantly elevated in OS tissues and cell lines, and increased ASB16-AS1 expression was related to patients' tumor size, TNM stage, and distant metastasis. The overall survival rate of OS patients presenting high ASB16-AS1 expression was shorter than that of patients presenting low ASB16-AS1 expression. Reduced ASB16-AS1 expression inhibited OS cell proliferation, migration, and invasion; promoted cell apoptosis; and impaired tumor growth in vivo. Mechanistically, ASB16-AS1 served as a sponge for miR-760 and positively modulated the expression of its target HDGF. Finally, inhibiting miR-760 and restoring HDGF expression abolished the impacts of ASB16-AS1 knockdown on the malignant characteristics of OS cells.

CONCLUSION

ASB16-AS1 is a novel oncogenic lncRNA in OS cells. ASB16-AS1 increased HDGF expression by sponging miR-760, thereby conferring cancer-promoting roles in OS. ASB16-AS1 is a potential early diagnostic and therapeutic target in OS.

摘要

目的

ASB16反义RNA1(ASB16-AS1)是一种与癌症相关的长链非编码RNA,它促进肿瘤发生和肿瘤发展。然而,据我们所知,ASB16-AS1是否以及如何参与骨肉瘤(OS)的恶性进程仍不清楚,因此值得探索。我们当前的研究聚焦于对骨肉瘤中ASB16-AS1进行深入研究。在本研究中,分析了ASB16-AS1在骨肉瘤组织和细胞系中的表达模式。此外,我们检测了ASB16-AS1对骨肉瘤患者的临床价值。此外,我们还探究了ASB16-AS1在体外和体内对骨肉瘤细胞恶性表型的影响及其潜在机制。

方法

采用逆转录定量PCR检测ASB16-AS1、微小RNA-760(miR-760)和肝癌衍生生长因子(HDGF)的表达。分别使用CCK-8和流式细胞术分析评估细胞增殖和凋亡,并通过细胞迁移和侵袭实验测定细胞迁移和侵袭能力。

结果

ASB16-AS1在骨肉瘤组织和细胞系中的表达显著升高,ASB16-AS1表达增加与患者的肿瘤大小、TNM分期和远处转移有关。ASB16-AS1高表达的骨肉瘤患者的总生存率低于ASB16-AS1低表达的患者。ASB16-AS1表达降低抑制了骨肉瘤细胞的增殖、迁移和侵袭;促进了细胞凋亡;并在体内损害了肿瘤生长。机制上,ASB16-AS1作为miR-760的海绵,正向调节其靶标HDGF的表达。最后,抑制miR-760并恢复HDGF表达消除了ASB16-AS1敲低对骨肉瘤细胞恶性特征的影响。

结论

ASB16-AS1是骨肉瘤细胞中一种新的致癌长链非编码RNA。ASB16-AS1通过吸附miR-760增加HDGF表达,从而在骨肉瘤中发挥促癌作用。ASB16-AS1是骨肉瘤潜在的早期诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e39/7081065/977c9cd269f5/OTT-13-2261-g0008.jpg
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