Department of Gynecology and obstetrics, the Fourth Hospital of Jinan, Jinan, Shandong, China.
Department of Laboratory Medicine, the Fourth Hospital of Jinan, Jinan, Shandong, China.
J Cell Biochem. 2019 Aug;120(8):12618-12627. doi: 10.1002/jcb.28528. Epub 2019 Mar 4.
High-grade ovarian serous carcinoma (HGS-OvCa), a type of ovarian cancer with poor prognosis due to distant metastasis, is urgently in need of new therapeutic targets. microRNAs (miRNAs), a class of small noncoding RNAs, perform significant roles in tumor progression. Mounting evidence has revealed the aberrant expression of miRNA in various cancers, one of which is HGS-OvCa. Present study planned to investigate that miRNA-301b-3p accelerates migration and invasion of high-grade ovarian serous tumor via targeting CPEB3/EGFR axis. Upregulation of miR-301b-3p was uncovered in HGS-OvCa tissues and cell lines, and was identified to be associated with metastasis. The Kaplan-Meier analysis confirmed the association of miR-301b-3p with poor prognosis of HGS-OvCa patients. Transwell assay validated the oncogenic effect of miR-301b-3p on migration and invasion of HGS-OvCa cells. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) was then identified as a target of miR-301b-3p. It was also discovered that CPEB3 was downregulated in HGS-OvCa tissues and cell lines. The Spearman correlation curve presented the negative correlation of CPEB3 expression with miR-301b-3p. Furthermore, rescue assays proved that miRNA-301b-3p regulated the invasion and migration through CPEB3. Western blot and qRT-PCR analysis showed that miRNA-301b-3p induced epidermal growth factor receptor and downstream metastasis-related proteins, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2), through CPEB3. To be concluded, these results indicated that miRNA-301b-3p accelerated migration and invasion of high-grade ovarian serous tumor via targeting CPEB3/EGFR axis.
高级别卵巢浆液性癌（HGS-OvCa）是一种预后不良的卵巢癌，其特征是远处转移，因此迫切需要新的治疗靶点。微小 RNA（miRNA）是一类小的非编码 RNA，在肿瘤进展中发挥重要作用。越来越多的证据表明，miRNA 在各种癌症中存在异常表达，其中之一就是 HGS-OvCa。本研究旨在探讨 miRNA-301b-3p 通过靶向 CPEB3/EGFR 轴加速高级别卵巢浆液性肿瘤的迁移和侵袭。研究发现 HGS-OvCa 组织和细胞系中存在 miR-301b-3p 的上调，且与转移相关。Kaplan-Meier 分析证实 miR-301b-3p 与 HGS-OvCa 患者的不良预后相关。Transwell 实验验证了 miR-301b-3p 对 HGS-OvCa 细胞迁移和侵袭的致癌作用。随后发现细胞质多聚腺苷酸化元件结合蛋白 3（CPEB3）是 miR-301b-3p 的靶标。还发现 CPEB3 在 HGS-OvCa 组织和细胞系中下调。Spearman 相关曲线显示 CPEB3 表达与 miR-301b-3p 呈负相关。此外，挽救实验证明 miR-301b-3p 通过 CPEB3 调节侵袭和迁移。Western blot 和 qRT-PCR 分析显示，miRNA-301b-3p 通过 CPEB3 诱导表皮生长因子受体和下游与转移相关的蛋白 p38 和细胞外信号调节激酶 1/2（ERK1/2）。综上所述，这些结果表明，miRNA-301b-3p 通过靶向 CPEB3/EGFR 轴加速高级别卵巢浆液性肿瘤的迁移和侵袭。
