Purpose

Owing to the late diagnosis and frequent metastasis, ovarian cancer (OC) exhibits a high mortality rate. The study was intended to figure out the function of long non-coding RNA (lncRNA) HCP5 in OC metastasis.

Methods

Microarray analysis was conducted to probe aberrantly expressed lncRNAs in OC tissues. Artificial silencing of lncRNA HCP5 was introduced in OC cells to identify its role in cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT). The potential downstream targets of lncRNA HCP5 were predicted by bio-information system and validated through dual luciferase reporter gene assays. Silencing of microRNA-525–5p (miR-525–5p) was introduced in cells to probe its role in cell behaviors. Xenograft tumors were induced in nude mice for in vivo experiments.

Results

High expression of lncRNA HCP5 was found in OC tissues and cells. Silencing of lncRNA HCP5 led to a decrease in cell proliferation, invasion, migration and EMT process. LncRNA HCP5 is mainly sub-localized in cytoplasm. LncRNA HCP5 could act as a sponge for miR-525–5p, which could further bind to polycomb repressive complex 1 (PRC1). Knockdown of miR-525–5p partly recovered the biological behaviors of OC cells inhibited by HCP5 silencing. In addition, HCP5 promoted Wnt/β-catenin signaling pathway activity. Silencing of lncRNA HCP5 also impeded growth and metastasis of tumor in mice.

Conclusion

The study suggested that lncRNA HCP5 might promote malignant behaviors of OC cells through the miR-525–5p/PRC1 crosstalk and the Wnt/β-catenin pathway. Silencing of HCP5 might serve as a novel option for OC treatment.

中文翻译：

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lncRNAHCP5 / microRNA-525-5p / PRC1串扰在卵巢癌细胞恶性行为中的作用。

目的

由于诊断晚和转移频繁，卵巢癌（OC）表现出很高的死亡率。这项研究旨在弄清长非编码RNA（lncRNA）HCP5在OC转移中的功能。

方法

进行微阵列分析以探测OC组织中异常表达的lncRNA。在OC细胞中引入了lncRNA HCP5的人工沉默，以鉴定其在细胞生存力，侵袭，迁移和上皮-间质转化（EMT）中的作用。通过生物信息系统预测了lncRNA HCP5的潜在下游靶标，并通过双重萤光素酶报告基因实验对其进行了验证。将microRNA-525-5p（miR-525-5p）沉默引入细胞中，以探究其在细胞行为中的作用。在裸鼠中诱导异种移植肿瘤用于体内实验。

结果

在OC组织和细胞中发现了lncRNA HCP5的高表达。lncRNA HCP5沉默导致细胞增殖，侵袭，迁移和EMT过程减少。LncRNA HCP5主要位于细胞质中。LncRNA HCP5可以充当miR-525-5p的海绵，它可以进一步与多梳抑制复合物1（PRC1）结合。抑制miR-525-5p可以部分恢复受到HCP5沉默抑制的OC细胞的生物学行为。另外，HCP5促进了Wnt /β-catenin信号通路活性。lncRNA HCP5沉默也阻碍了小鼠肿瘤的生长和转移。

结论

研究表明，lncRNA HCP5可能通过miR-525-5p / PRC1串扰和Wnt /β-catenin途径促进OC细胞的恶性行为。HCP5沉默可能是OC治疗的新选择。