Department of Reproduction Center, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China.
Xuzhou Prison Hospital of Jiangsu Province, Xuzhou, China.
J Cell Physiol. 2020 Apr;235(4):3939-3949. doi: 10.1002/jcp.29289. Epub 2019 Oct 9.
Ovarian cancer (OC) is a highly prevalent gynecologic malignancy and its mortality is extremely high. Therefore, the development of novel therapeutic approaches for OC is of great significance. In this study, LINC01342 was upregulated in OC tissue in the GSE38666 microarray and in tumor tissue samples collected in our center. The silencing of LINC01342 suppressed the proliferative and metastatic capacities of A2780 and HO8910 cells. Subcellular distribution assays showed that LINC01342 was mainly enriched in the cytoplasm. Subsequently, the downregulation of microRNA-30c-2-3p was proven to be the target of LINC01342. The silencing of microRNA-30c-2-3p enhanced the clonality and migratory capacity of OC cells. Moreover, the silencing of microRNA-30c-2-3p could reverse the inhibited migration and clonality in OC cells caused by LINC01342 knockdown. In addition, hypoxia-inducible factor 3 subunit α (HIF3A) was proven to be the target gene of microRNA-30c-2-3p, which was upregulated. HIF3A was negatively regulated by microRNA-30c-2-3p but positively regulated by LINC01342 in OC cells. An RNA binding protein immunoprecipitation assay showed that microRNA-30c-2-3p, LINC01342, and HIF3A could bind to argonaute RISC catalytic component 2. The overexpression of HIF3A reversed the inhibited migration and clonality in OC cells with LINC01342 knockdown. By analyzing the follow-up data from the enrolled OC patients, the LINC01342 and HIF3A levels were negatively correlated with prognosis, while the microRNA-30c-2-3p level was positively correlated with the same. In short, the upregulated LINC01342 in OC absorbs microRNA-30c-2-3p to release HIF3A. Thus, upregulated HIF3A expression accelerates the progression of OC.
卵巢癌（OC）是一种高发的妇科恶性肿瘤，其死亡率极高。因此，开发治疗 OC 的新方法具有重要意义。本研究在 GSE38666 微阵列中发现 LINC01342 在 OC 组织中上调，并在我们中心收集的肿瘤组织样本中上调。LINC01342 的沉默抑制了 A2780 和 HO8910 细胞的增殖和转移能力。亚细胞分布试验表明，LINC01342 主要富集在细胞质中。随后，证明 microRNA-30c-2-3p 的下调是 LINC01342 的靶标。microRNA-30c-2-3p 的沉默增强了 OC 细胞的克隆性和迁移能力。此外，沉默 microRNA-30c-2-3p 可以逆转 LINC01342 敲低引起的 OC 细胞迁移和克隆性抑制。此外，证明缺氧诱导因子 3 亚基α（HIF3A）是 microRNA-30c-2-3p 的靶基因，该基因上调。在 OC 细胞中，HIF3A 受 microRNA-30c-2-3p 的负调控，受 LINC01342 的正调控。RNA 结合蛋白免疫沉淀试验表明，microRNA-30c-2-3p、LINC01342 和 HIF3A 可以与 Argonaute RISC 催化成分 2 结合。HIF3A 的过表达逆转了 LINC01342 敲低的 OC 细胞中抑制的迁移和克隆性。通过分析纳入的 OC 患者的随访数据，LINC01342 和 HIF3A 水平与预后呈负相关，而 microRNA-30c-2-3p 水平与预后呈正相关。总之，OC 中上调的 LINC01342 吸收 microRNA-30c-2-3p 释放 HIF3A。因此，上调的 HIF3A 表达加速了 OC 的进展。
