Long Noncoding RNA LINC01133 Functions as an miR-422a Sponge to Aggravate the Tumorigenesis of Human Osteosarcoma.
Long Noncoding RNA LINC01133 Functions as an miR-422a Sponge to Aggravate the Tumorigenesis of Human Osteosarcoma.
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DOI：
10.3727/096504017x14907375885605
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发表时间：
2018-04-10
影响因子：
3.1
通讯作者：
Feng FB
中科院分区：
文献类型：
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作者：
Zeng HF;Qiu HY;Feng FB
长链非编码rna （Long noncoding RNAs, lncRNAs）已被证实参与多种类型的恶性肿瘤，包括骨肉瘤（osteosarcoma， OS），骨肉瘤是最常见的原发性骨肿瘤，发病率突出。尽管越来越多的lncrna被报道介导OS的发生，但潜在的机制仍不清楚。本研究旨在揭示lncRNA LINC01133作为miRNA海绵介导OS致瘤性的机制。在本研究中，我们发现与非癌组织和正常人成骨细胞系相比，LINC01133在OS肿瘤组织和细胞系中的表达水平有统计学上调。沉默LINC01133也能明显抑制OS细胞（HOS和U2-OS）的增殖、迁移和侵袭。生物信息学分析预测LINC01133特异性靶向miR-422a，并通过双荧光素酶报告基因试验验证。此外，功能实验显示miR-422a在OS进展中发挥肿瘤抑制作用，并能有效逆转LINC01133的功能。综上所述，我们的研究发现lncRNA LINC01133通过海绵化miR-422a加重OS的增殖、迁移和侵袭，这为OS的肿瘤发生提供了新的认识。
Long noncoding RNAs (lncRNAs) have been verified to participate in various types of malignant tumors, including osteosarcoma (OS), which is the most common primary bone tumor with outstanding morbidity. Although an increasing number of lncRNAs have been reported to mediate the occurrence of OS, the potential mechanisms are still unclear. This study intends to uncover the mechanism by which lncRNA LINC01133 functions as an miRNA sponge to mediate OS tumorigenicity. In this study, we found that the expression level of LINC01133 was statistically upregulated in OS tumor tissue and cell lines compared to noncancerous tissues and a normal human osteoplastic cell line. LINC01133 silencing could also observably suppress the proliferation, migration, and invasion of OS cells (HOS and U2-OS). Bioinformatics analysis predicted that LINC01133 specifically targeted miR-422a, which was validated by dual-luciferase reporter assay. Furthermore, functional experiments revealed that miR-422a played a tumor-suppressive role in OS progression and could effectively reverse the function of LINC01133. In summary, our study discovered that lncRNA LINC01133 aggravates the proliferation, migration, and invasion of OS by sponging miR-422a, which provides a novel insight in the tumorigenesis of OS.