LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4.,Gene Therapy

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LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4.
Gene Therapy ( IF 4.6 ) Pub Date : 2020-02-10 , DOI: 10.1038/s41434-020-0123-2
Jianchu Wang ₁ , Qianli Tang _{1,

2} , Libai Lu ₁ , Zongjiang Luo ₁ , Wenchuan Li ₁ , Yuan Lu ₁ , Jian Pu ₁

Affiliation

Long noncoding RNA OIP5-AS1 has been observed to be increased in several cancers, however, its role and biological mechanism was poorly understood in HCC. Currently, we found OIP5-AS1 expression was upregulated in HCC cells compared with normal human liver cells. Knockdown of OIP5-AS1 suppressed HCC cell proliferation, induced cells cycle arrest and cells apoptosis. In addition, HCC cell migration and invasion capacity in vitro were also inhibited by OIP5-AS1 inhibition. Bioinformatics analysis revealed OIP5-AS1 could interact with miR-363-3p, thereby repressing HCC development. We also observed miR-363-3p was significantly decreased in HCC cells and overexpression of miR-363-3p repressed HCC progression. The correlation between OIP5-AS1 and miR-363-3p was confirmed by performing RIP assay and RNA pull-down assay. Subsequently, SOX4 was predicted as a target of miR-363-3p and miR-363-3p modulated SOX4 levels negatively in vitro. Apart from these, in vivo experiments established that OIP5-AS1 can suppress HCC development through regulating miR-363-3p and SOX4. Collectively, these demonstrated that OIP5-AS1 was involved in HCC progression via targeting miR-363-3p and SOX4. OIP5-AS1 can act as a novel candidate for HCC diagnosis, prognosis, and therapy.

中文翻译：

LncRNA OIP5-AS1 与 miR-363-3p 相互作用，通过上调 SOX4 促进肝细胞癌的进展。

已观察到长链非编码 RNA OIP5-AS1 在几种癌症中增加，然而，其在 HCC 中的作用和生物学机制知之甚少。目前，我们发现与正常人肝细胞相比，HCC 细胞中 OIP5-AS1 的表达上调。敲除 OIP5-AS1 可抑制 HCC 细胞增殖，诱导细胞周期停滞和细胞凋亡。此外，体外 HCC 细胞迁移和侵袭能力也受到 OIP5-AS1 抑制的抑制。生物信息学分析显示 OIP5-AS1 可以与 miR-363-3p 相互作用，从而抑制 HCC 的发展。我们还观察到 miR-363-3p 在 HCC 细胞中显着降低，并且 miR-363-3p 的过表达抑制了 HCC 进展。OIP5-AS1 和 miR-363-3p 之间的相关性通过 RIP 测定和 RNA 下拉测定得到证实。随后，SOX4 被预测为 miR-363-3p 的靶标，而 miR-363-3p 在体外负向调节 SOX4 水平。除此之外，体内实验证实 OIP5-AS1 可以通过调节 miR-363-3p 和 SOX4 来抑制 HCC 的发展。总的来说，这些表明 OIP5-AS1 通过靶向 miR-363-3p 和 SOX4 参与 HCC 进展。OIP5-AS1 可以作为 HCC 诊断、预后和治疗的新候选者。

更新日期：2020-02-10

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