Background

Circular RNAs (circRNAs) have recently been identified in the development and progression of multiple human diseases. However, the significance of circRNAs in uterine leiomyoma (ULM) remains to be elucidated. Here, we aim to explore the expression profile of circRNAs in ULM and the potential of cicRNAs to be used as biomarkers or therapeutic targets.

Methods

Global circRNA expression Profiles for ULM was performed by microarray in ULM tissue and matched adjacent normal myometrium counterpart. Bioinformatics analysis, qRT-PCR validation, and receiver operating characteristic (ROC) diagnostic accuracy was applied for differentially expressed circRNAs. Cell proliferation and spheroid formation assay were performed to assess the functional role of candidate circRNA.

Results

579 up- and 625 down-regulated circRNAs were identified between ULMs and adjacent normal myometrium tissues. Bioinformatics analysis suggested that most differentially expressed circRNAs participate in pathways were related to pathological processes of ULM. The qRT-PCR validation results for 6 circRNAs (hsa_circ_0083920, hsa_circ_0056686, hsa_circ_0062558, hsa_circ_0020376, hsa_circ_0043597, hsa_circ_0026353, and circ_0017248) matched the microarray results. ROC analysis showed that hsa_circ_0083920, hsa_circ_0056686, hsa_circ_0062558, hsa_circ_0020376, and hsa_circ_0043597 could accurately distinguish the ULM samples from the myometrium samples. Additionally, hsa_circ_0056686 was validated to be upregulated in ULM and was associated with the leiomyoma size (P = 0.0446). Reduction of endogenous hsa_circ_0056686 expression significantly suppressed leiomyoma cell proliferation and spheroid formation capacity.

Conclusions

This study provides an integrated analysis of circRNAs in ULM, and gives new insight into the complex epigenetic mechanisms of ULM. Aberrantly expressed circRNAs may contribute to the pathogenesis of ULM and hsa_circ_0056686 might be a potential therapeutic target.

背景

最近在多种人类疾病的发展和进展中发现了环状 RNA（circRNA）。然而，circRNAs在子宫平滑肌瘤（ULM）中的意义仍有待阐明。在这里，我们旨在探索 circRNA 在 ULM 中的表达谱以及 cicRNA 作为生物标志物或治疗靶点的潜力。

方法

ULM 的全局 circRNA 表达谱是通过 ULM 组织中的微阵列和匹配的相邻正常子宫肌层对应物进行的。生物信息学分析、qRT-PCR 验证和接受者操作特征 (ROC) 诊断准确性适用于差异表达的 circRNA。进行细胞增殖和球体形成测定以评估候选 circRNA 的功能作用。

结果

在 ULM 和邻近的正常子宫肌层组织之间鉴定出 579 个上调和 625 个下调的 circRNA。生物信息学分析表明，大多数差异表达的circRNA参与的通路与ULM的病理过程有关。6 个 circRNA（hsa_circ_0083920、hsa_circ_0056686、hsa_circ_0062558、hsa_circ_0020376、hsa_circ_0043597、hsa_circ_0026353）的 qRT-PCR 验证结果与 24 微阵列结果相匹配。ROC分析表明，hsa_circ_0083920、hsa_circ_0056686、hsa_circ_0062558、hsa_circ_0020376和hsa_circ_0043597可以准确地区分ULM样本和子宫肌层样本。此外，hsa_circ_0056686 被证实在 ULM 中上调并且与平滑肌瘤大小相关（P = 0.0446）。内源性 hsa_circ_0056686 表达的减少显着抑制了平滑肌瘤细胞增殖和球体形成能力。

结论

这项研究提供了 ULM 中 circRNA 的综合分析，并为 ULM 复杂的表观遗传机制提供了新的见解。异常表达的 circRNA 可能有助于 ULM 的发病机制，hsa_circ_0056686 可能是一个潜在的治疗靶点。