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长链非编码 RNA NR2F1-AS1 通过 miR-485-5p/miR-218-5p/BIRC5 轴促进骨肉瘤细胞的恶性表型。

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis.

机构信息

Department of Foot and Ankle Surgery, Zhengzhou Orthopedics Hospital, Zhengzhou, Henan 450052, P.R. China.

Department of Laboratory, Zhengzhou Orthopedics Hospital, Zhengzhou, Henan 450052, P.R. China.

出版信息

Oncol Rep. 2020 Oct;44(4):1583-1595. doi: 10.3892/or.2020.7698. Epub 2020 Jul 20.

Abstract

Long non‑coding RNA (lncRNA) NR2F1 antisense RNA 1 (NR2F1‑AS1) has been reported to be an oncogene in several cancer types, including osteosarcoma (OS). However, the underlying fundamental molecular mechanism of NR2F1‑AS1 in OS remains largely unknown, which the present study aimed to elucidate. The present study demonstrated that NR2F1‑AS1 expression is markedly increased in OS, and NR2F1‑AS1 was shown to exert oncogenic functions in OS. Further molecular mechanistic studies revealed that microRNA (miR)‑485‑5p and miR‑218‑5p were direct targets of NR2F1‑AS1. More importantly, miR‑485‑5p and miR‑218‑5p exhibited low expression levels and were negatively correlated with NR2F1‑AS1 expression in OS tissues. It was then identified that baculoviral inhibitor of apoptosis repeat‑containing 5 (BIRC5) was a direct target of miR‑485‑5p and miR‑218‑5p in OS cells. Furthermore, a series of experiments suggested that NR2F1‑AS1 affects the proliferation, migration, invasion and apoptosis of OS cells by regulating BIRC5. Finally, it was revealed that silencing of NR2F1‑AS1 repressed the OS cell malignant phenotype by binding with miR‑485‑5p and miR‑218‑5p, and then downregulating BIRC5 expression, which suggests that the NR2F1‑AS1/miR‑485‑5p/miR‑218‑5p/BIRC5 axis could be a potential target for treating OS.

摘要

长链非编码 RNA(lncRNA)NR2F1 反义 RNA 1(NR2F1-AS1)已被报道在多种癌症类型中是一种癌基因,包括骨肉瘤(OS)。然而,NR2F1-AS1 在 OS 中的潜在基本分子机制在很大程度上仍然未知,本研究旨在阐明这一机制。本研究表明,NR2F1-AS1 在 OS 中表达明显增加,并且 NR2F1-AS1 在 OS 中发挥致癌作用。进一步的分子机制研究表明,微小 RNA(miR)-485-5p 和 miR-218-5p 是 NR2F1-AS1 的直接靶标。更重要的是,miR-485-5p 和 miR-218-5p 在 OS 组织中的表达水平较低,与 NR2F1-AS1 的表达呈负相关。随后确定,杆状病毒凋亡抑制剂重复包含 5(BIRC5)是 OS 细胞中 miR-485-5p 和 miR-218-5p 的直接靶标。此外,一系列实验表明,NR2F1-AS1 通过调节 BIRC5 影响 OS 细胞的增殖、迁移、侵袭和凋亡。最后,研究揭示了沉默 NR2F1-AS1 通过与 miR-485-5p 和 miR-218-5p 结合,然后下调 BIRC5 表达,从而抑制 OS 细胞恶性表型,表明 NR2F1-AS1/miR-485-5p/miR-218-5p/BIRC5 轴可能是治疗 OS 的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27ef/7448419/d66465bb634a/OR-44-04-1583-g00.jpg

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