Department of Gynecology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570011, Hainan, PR China.
Department of Stomatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570011, Hainan, PR China.
J Ovarian Res. 2021 Nov 13;14(1):154. doi: 10.1186/s13048-021-00917-7.
Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved.
Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells.
Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability.
This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.
环状 RNA（circRNAs）越来越被认为是包括卵巢癌（OC）在内的癌症的重要调控因子。本研究重点关注 circ_0000745 对 OC 发展的影响及其涉及的分子。
通过 RT-qPCR 检测收集的 OC 组织和获得的 OC 细胞系中 circ_0000745 的表达。用 RNase R 处理检测 circ_0000745 在细胞中的稳定性。使用生物信息系统预测与 circ_0000745 相互作用的靶转录物。进行 circ_0000745、microRNA（miR）-3187-3p 和 erb-b2 受体酪氨酸激酶 4（ERBB4）的功能获得和缺失研究，以确定它们对 OC 细胞增殖、迁移、侵袭和干细胞特性的功能。
circ_0000745 和 ERBB4 在 OC 组织和细胞中大量表达，而 miR-3187-3p 表达水平较低。circ_0000745 与 miR-3187-3p 结合并阻断其对 ERBB4 的抑制作用。下调 circ_0000745 降低了 SK-OV-3 细胞的增殖、侵袭、上皮-间充质转化和干细胞特性，但 miR-3187-3p 抑制或 ERBB4 上调可阻断这种降低。相反，人工诱导 circ_0000745 上调、miR-3187-3p 上调和 ERBB4 下调导致 ES-2 细胞出现相反的趋势。ERBB4 促进了 PI3K/AKT 信号通路的磷酸化。发现 RNA 结合蛋白 IGF2BP2 与 circ_0000745 结合并促进其表达和稳定性。
本研究表明，IGF2BP2 上调的 circ_0000745 通过 miR-3187-3p/ERBB4/PI3K/AKT 轴促进 OC 细胞的侵袭和干细胞特性。circ_0000745 可能成为 OC 治疗的一个有前途的靶点。
