The Second Department of Otolaryngology, Head and Neck Surgery of The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Kaohsiung J Med Sci. 2021 Aug;37(8):686-698. doi: 10.1002/kjm2.12381. Epub 2021 May 4.
Nasopharyngeal carcinoma (NPC) is the most common type of human malignant tumor in the head and neck, and tumor angiogenesis is essential for its development. Here, we showed that the circRNA ZNF609/microRNA (miR)-145/Stathmin 1 (STMN1) axis regulated angiogenesis in NPC.Circ-ZNF609, miR-145, and STMN1 expression in NPC cells and NPC samples were examined using qRT-PCR. The protein levels of STMN1, VEGFR1, and VEGFR2 were evaluated using western blotting. VEGF level was determined by ELISA. The proliferation of NPC cells and HUVECs was examined using a CCK-8 assay. Transwell assays and wound-healing assays were applied to assess the migration of NPC cells and HUVECs, respectively. Angiogenesis of HUVECs was evaluated by an angiogenesis assay. In addition, a dual-luciferase reporter assay and RNA pull-down assays were employed to verify the binding relationship between circ-ZNF609 and miR-145 as well as between miR-145 and STMN1. Here, we showed that circ-ZNF609 and STMN1 expression was increased, while miR-145 expression was decreased in NPC cells and NPC samples. Circ-ZNF609 may negatively regulate miR-145 expression by acting as a ceRNA. Silencing circ-ZNF609 suppressed cell proliferation, migration, and angiogenesis in NPC, while knockdown of miR-145 reversed these effects. In addition, we found that STMN1 was the downstream target of miR-145. MiR-145 overexpression suppressed cell proliferation, migration, and angiogenesis in NPC, which was abolished by STMN1 overexpression. Our data suggested that circ-ZNF609 promotes cell proliferation, migration, and angiogenesis in NPC by upregulating the expression of STMN1 by sponging miR-145 in NPC.
鼻咽癌（NPC）是头颈部最常见的人类恶性肿瘤类型，肿瘤血管生成对其发展至关重要。在这里，我们表明 circRNA ZNF609/微小 RNA（miR）-145/Stathmin 1（STMN1）轴调节 NPC 中的血管生成。使用 qRT-PCR 检查 NPC 细胞和 NPC 样本中的 circ-ZNF609、miR-145 和 STMN1 的表达。使用 Western blot 评估 STMN1、VEGFR1 和 VEGFR2 的蛋白水平。通过 ELISA 测定 VEGF 水平。使用 CCK-8 测定 NPC 细胞和 HUVEC 的增殖。应用 Transwell 测定和划痕愈合测定分别评估 NPC 细胞和 HUVEC 的迁移。通过血管生成测定评估 HUVEC 的血管生成。此外，使用双荧光素酶报告基因测定和 RNA 下拉测定验证 circ-ZNF609 与 miR-145 以及 miR-145 与 STMN1 之间的结合关系。在这里，我们表明 circ-ZNF609 和 STMN1 的表达增加，而 miR-145 的表达在 NPC 细胞和 NPC 样本中降低。Circ-ZNF609 可能通过充当 ceRNA 来负调控 miR-145 的表达。沉默 circ-ZNF609 抑制 NPC 中的细胞增殖、迁移和血管生成，而 miR-145 的敲低则逆转了这些效应。此外，我们发现 STMN1 是 miR-145 的下游靶标。miR-145 过表达抑制 NPC 中的细胞增殖、迁移和血管生成，而 STMN1 过表达则消除了这种抑制作用。我们的数据表明，circ-ZNF609 通过在 NPC 中上调 STMN1 的表达来促进 NPC 中的细胞增殖、迁移和血管生成，这是通过吸附 miR-145 来实现的。
