The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China.
Cell Cycle. 2024 Mar;23(6):693-702. doi: 10.1080/15384101.2024.2357909. Epub 2024 Jun 12.
Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of tumor-related deaths in China. Circ_0050444 has been revealed to be downregulated in ESCC tissues, however, its function and molecular mechanism underlying ESCC progression is unknown. Therefore, we attempted to clarify the functional role and molecular mechanism of circ_0050444 underlying ESCC progression. RT-qPCR and RNase R digestion assays were used to evaluate circ_0050444 expression and stability characteristics in ESCC cells. Gain-of-function assays were conducted to clarify circ_0050444 role in ESCC cell malignant behaviors. Bioinformatics and mechanism experiments were performed to assess the relationship between circ_0050444 or C10orf91 and miR-486-3p in ESCC cells. Rescue assays were conducted to evaluate the regulatory function of the circ_0050444-miR-486-3p-C10orf91 axis in ESCC cellular processes. Circ_0050444 expression was found to be downregulated both in ESCC patient tissues and cell lines. Functionally, circ_0050444 overexpression repressed ESCC cell proliferative, migratory, and invasive capabilities in cultured cells. Mechanistically, circ_0050444 was found to be competitively bound with miR-486-3p to upregulate C10orf91 in ESCC cells. Moreover, the impact of circ_0050444 elevation on ESCC cell proliferation, migration, and invasion was countervailed by C10orf91 silencing. Circ_0050444 presents downregulation and functions as a tumor suppressor in ESCC progression. Circ_0050444 suppresses ESCC proliferation, migration, and invasion through sponging miR-486-3p to upregulate C10orf91, providing a potential new direction for seeking therapeutic plans for ESCC.
食管鳞状细胞癌（ESCC）是中国肿瘤相关死亡的第四大主要原因。Circ_0050444 在 ESCC 组织中被发现下调，但其在 ESCC 进展中的功能和分子机制尚不清楚。因此，我们试图阐明 Circ_0050444 在 ESCC 进展中的功能作用和分子机制。使用 RT-qPCR 和 RNase R 消化测定来评估 ESCC 细胞中 Circ_0050444 的表达和稳定性特征。进行功能获得实验以阐明 Circ_0050444 在 ESCC 细胞恶性行为中的作用。进行生物信息学和机制实验来评估 ESCC 细胞中 Circ_0050444 或 C10orf91 与 miR-486-3p 之间的关系。进行挽救实验来评估 circ_0050444-miR-486-3p-C10orf91 轴在 ESCC 细胞过程中的调节功能。发现 Circ_0050444 在 ESCC 患者组织和细胞系中均表达下调。功能上，Circ_0050444 的过表达抑制了培养细胞中 ESCC 细胞的增殖、迁移和侵袭能力。从机制上讲，在 ESCC 细胞中发现 Circ_0050444 与 miR-486-3p 竞争结合以上调 C10orf91。此外，沉默 C10orf91 可以抵消 Circ_0050444 升高对 ESCC 细胞增殖、迁移和侵袭的影响。Circ_0050444 在 ESCC 进展中呈现下调并发挥肿瘤抑制作用。Circ_0050444 通过海绵吸附 miR-486-3p 来抑制 ESCC 的增殖、迁移和侵袭，为寻求 ESCC 的治疗方案提供了一个新的潜在方向。
