Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Respiratory and Critical Care Medicine, Nanyang Central Hospital, Nanyang, Henan, China.
Thorac Cancer. 2022 Apr;13(7):934-946. doi: 10.1111/1759-7714.14326. Epub 2022 Mar 20.
Circular RNAs (circRNAs) are implicated in the progression and radiosensitivity of human cancers, including esophageal carcinoma (ESCA). In this study, we aimed to explore the functions of circRNA 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (circATIC) in ESCA progression.
CircATIC expression, miR-10b-3p and Rh family C glycoprotein (RHCG) were examined via quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay. 5'-ethynyl-2'-deoxyuridine (EdU), wound-healing, transwell, and cell colony formation assays and flow cytometry analysis were conducted to evaluate cell proliferation, migration, invasion, radiosensitivity and apoptosis, respectively. Dual-luciferase reporter assay and RNA pulldown assay were conducted to analyze the relationships among circATIC, miR-10b-3p and RHCG. A murine xenograft model assay was performed to explore the functions of circATIC in tumor formation and radiosensitivity in vivo.
CircATIC was decreased in ESCA. CircATIC overexpression suppressed cell proliferation, migration and invasion and promoted radiosensitivity and apoptosis in ESCA cells in vitro and repressed tumor formation and radioresistance in vivo. Functionally, circATIC served as the sponge for miR-10b-3p, which directly targeted RHCG. MiR-10b-3p elevation reversed circATIC-mediated effect on ESCA cell progression. Moreover, miR-10b-3p inhibition suppressed cell growth and metastasis and enhanced radiosensitivity in ESCA cells by targeting RHCG.
Overexpression of circATIC hampered ESCA progression and promoted radiosensitivity depending on the regulation of miR-10b-3p and RHCG.
环状 RNA（circRNA）参与了包括食管癌（ESCA）在内的多种人类癌症的进展和放射敏感性。在这项研究中，我们旨在探索 5-氨基咪唑-4-甲酰胺核苷酸 formyltransferase/IMP 环化水解酶（circATIC）在 ESCA 进展中的作用。
通过定量实时聚合酶链反应（qRT-PCR）、western blot 检测或免疫组织化学（IHC）检测，检测 circATIC 的表达、miR-10b-3p 和 Rh 家族 C 糖蛋白（RHCG）。通过 5-乙炔基-2'-脱氧尿苷（EdU）、划痕愈合、Transwell 和细胞集落形成实验以及流式细胞术分析，分别评估细胞增殖、迁移、侵袭、放射敏感性和凋亡。双荧光素酶报告基因检测和 RNA 下拉实验分析 circATIC、miR-10b-3p 和 RHCG 之间的关系。进行小鼠异种移植模型实验以研究 circATIC 在体内肿瘤形成和放射敏感性中的作用。
circATIC 在 ESCA 中表达下调。circATIC 的过表达抑制 ESCA 细胞的体外增殖、迁移和侵袭，并促进放射敏感性和凋亡，同时抑制体内肿瘤形成和放射抗性。功能上，circATIC 作为 miR-10b-3p 的海绵，直接靶向 RHCG。miR-10b-3p 的上调逆转了 circATIC 对 ESCA 细胞进展的调控作用。此外，miR-10b-3p 的抑制通过靶向 RHCG 抑制 ESCA 细胞的生长和转移，并增强放射敏感性。
circATIC 的过表达通过调节 miR-10b-3p 和 RHCG 来阻碍 ESCA 的进展并促进放射敏感性。
