Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Oncology, Hefei BOE Hospital, Hefei, Anhui, China.
Gen Thorac Cardiovasc Surg. 2023 Jan;71(1):33-45. doi: 10.1007/s11748-022-01874-8. Epub 2022 Oct 3.
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the gastrointestinal tract. Circular RNAs (circRNAs) are involved in the pathogenesis of cancer. This study aimed to elucidate the role and molecular mechanism of circ_0008726 in ESCC.
The expression levels of circ_0008726, microRNA (miR)-206 and homeobox A13 (HOXA13) were detected by quantitative real-time PCR (QRT-PCR). Cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays were conducted to detect the proliferative ability of ESCC cells. Apoptosis and invasion of ESCC cells were detected by flow cytometry and transwell assays. Tube formation assay was used to detect the angiogenesis of ESCC cells. The expression of related proteins was detected by western blot analysis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circ_0008726, miR-206 and HOXA13. Xenograft mice model was established to study the in vivo effect of circ_0008726 knockdown.
Expression of circ_0008726 was up-regulated in ESCC tissues and cells. Knockdown of circ_0008726 repressed proliferation, invasion, angiogenesis, and promoted apoptosis of ESCC cells. Circ_0008726 acted as a sponge for miR-206, and HOXA13 was a target of miR-206. The suppressive effects of circ_0008726 knockdown on cell proliferation, invasion, and angiogenesis were abated by miR-206 down-regulation. Meanwhile, overexpression of HOXA13 partially reversed the suppressive effects of miR-206 enrichment on ESCC cell malignant behaviors. Knockdown of circ_0008726 inhibited ESCC tumor growth in vivo.
In short, circ_0008726 exerted the carcinogenic effects to regulate the proliferation, invasion, angiogenesis and apoptosis of ESCC cells by targeting miR-206/HOXA13 axis.
食管鳞状细胞癌（ESCC）是最常见的胃肠道恶性肿瘤之一。环状 RNA（circRNA）参与癌症的发病机制。本研究旨在阐明 circ_0008726 在 ESCC 中的作用和分子机制。
通过实时定量 PCR（QRT-PCR）检测 circ_0008726、微小 RNA（miR）-206 和同源盒 A13（HOXA13）的表达水平。细胞计数试剂盒-8（CCK-8）和 5-乙炔基-2'-脱氧尿苷（EdU）测定法检测 ESCC 细胞的增殖能力。通过流式细胞术和 Transwell 测定法检测 ESCC 细胞的凋亡和侵袭。管形成测定法用于检测 ESCC 细胞的血管生成。通过 Western blot 分析检测相关蛋白的表达。双荧光素酶报告基因和 RNA 免疫沉淀（RIP）实验验证 circ_0008726、miR-206 和 HOXA13 之间的相互作用。建立异种移植小鼠模型研究 circ_0008726 敲低的体内作用。
circ_0008726 在 ESCC 组织和细胞中表达上调。circ_0008726 敲低抑制 ESCC 细胞的增殖、侵袭和血管生成，促进细胞凋亡。circ_0008726 作为 miR-206 的海绵，HOXA13 是 miR-206 的靶基因。circ_0008726 敲低对细胞增殖、侵袭和血管生成的抑制作用被 miR-206 下调所减弱。同时，miR-206 富集对 ESCC 细胞恶性行为的抑制作用被 HOXA13 的过表达部分逆转。circ_0008726 敲低抑制体内 ESCC 肿瘤生长。
总之，circ_0008726 通过靶向 miR-206/HOXA13 轴调节 ESCC 细胞的增殖、侵袭、血管生成和凋亡，发挥致癌作用。
