Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute in Guangdong Province, Guangzhou, 510150, China.
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Biomed Pharmacother. 2019 Jun;114:108832. doi: 10.1016/j.biopha.2019.108832. Epub 2019 Apr 11.
Circular RNAs are known to participate in tumorigenesis through a variety of pathways, and as such, have potential to serve as molecular markers in tumor diagnosis and treatment. Here, using quantitative reverse transcription (qRT)-PCR, we showed that circ-CSPP1 is highly expressed in ovarian cancer (OC) tissues. Particularly, we detected circ-CSPP1 expression in three OC cell lines; of which, OVCAR3 and A2780 demonstrated higher levels of circ-CSPP1 expression, and CAOV3 showed lower circ-CSPP1 expression level. Subsequent silencing of circ-CSPP1 in OVCAR3 and A2780 cell lines revealed decreased cell growth, migration and invasion, while overexpression of circ-CSPP1 caused opposite results We also found that miR-1236-3p is a target of circ-CSPP1. Circ-CSPP1 silencing increased the expression of miR-1236-3p, and circ-CSPP1 overexpression decreased miR-1236-3p expression. MiR-1236-3p reportedly plays a tumor-suppressor role in OC by targeting zinc finger E-box binding homeobox 1 (ZEB1). In agreement with this, we showed that silencing circ-CSPP1 significantly decreased ZEB1 expression at both RNA and protein levels, and epithelial-mesenchymal transition (EMT) related markers (E-cadherin and N-cadherin) varied with ZEB1 expression. Circ-CSPP1 silencing also caused decreased expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor A (VEGFA), both of which are related to tumorigenesis. Overexpression of circ-CSPP1 had opposite effects. In addition, we indicated that the tumor-promoting effect was inhibited after we transfected miR-1236-3p into circ-CSPP1 overexpressing OC cells. Altogether, our findings suggest that by acting as a miR-1236-3p sponge, circ-CSPP1 impairs the inhibitory effect of miR-1236-3p on ZEB1, which subsequently promotes EMT and OC development.
环状 RNA 已知通过多种途径参与肿瘤发生，因此具有作为肿瘤诊断和治疗的分子标志物的潜力。在这里，我们使用定量逆转录 (qRT)-PCR 显示 circ-CSPP1 在卵巢癌 (OC) 组织中高度表达。特别是，我们在三种 OC 细胞系中检测到 circ-CSPP1 的表达;其中，OVCAR3 和 A2780 显示出更高水平的 circ-CSPP1 表达，而 CAOV3 显示出更低水平的 circ-CSPP1 表达。随后在 OVCAR3 和 A2780 细胞系中沉默 circ-CSPP1 显示出细胞生长、迁移和侵袭减少，而 circ-CSPP1 的过表达则导致相反的结果。我们还发现 miR-1236-3p 是 circ-CSPP1 的靶标。circ-CSPP1 沉默增加了 miR-1236-3p 的表达，而过表达 circ-CSPP1 降低了 miR-1236-3p 的表达。据报道，miR-1236-3p 通过靶向锌指 E 盒结合同源盒 1 (ZEB1) 在 OC 中发挥肿瘤抑制作用。与这一结果一致，我们表明，沉默 circ-CSPP1 可显著降低 RNA 和蛋白质水平上的 ZEB1 表达，并且上皮-间充质转化 (EMT) 相关标志物 (E-钙粘蛋白和 N-钙粘蛋白) 随 ZEB1 表达而变化。circ-CSPP1 沉默还导致基质金属蛋白酶-2 (MMP-2) 和血管内皮生长因子 A (VEGFA) 的表达减少，这两者都与肿瘤发生有关。circ-CSPP1 的过表达则具有相反的效果。此外，我们表明，在将 miR-1236-3p 转染到过表达 circ-CSPP1 的 OC 细胞中后，肿瘤促进作用受到抑制。总之，我们的研究结果表明，circ-CSPP1 作为 miR-1236-3p 的海绵，可削弱 miR-1236-3p 对 ZEB1 的抑制作用，从而促进 EMT 和 OC 发展。
