Department of Oncology, Ningxiang People's Hospital, Ningxiang, China.
Thorac Cancer. 2023 Mar;14(9):794-804. doi: 10.1111/1759-7714.14809. Epub 2023 Feb 2.
Breast cancer (BC) is a common malignant tumor that threatens the health of women worldwide. Hsa_circ_0005273 has been identified as a carcinogenic factor in some solid tumors, including BC. However, the molecular mechanism of circ_0005273 in BC is poorly defined.
The expression of circ_0005273, miR-509-3p, and hyaluronan-mediated motility receptor (HMMR) mRNA in BC was detected by quantitative real-time polymerase chain reaction. Cell proliferation, migration, invasion, and apoptosis were detected by 5-ethynyl-2'-deoxyuridine, transwell, and flow cytometry assays. The glycolysis level was detected via specific kits. Western blot was used to detect protein expression. Binding between miR-509-3p and circ_0005273 or HMMR was also verified by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. Xenograft tumor model was used to detect tumor changes in mice, and immunohistochemistry assay was employed to detect Ki-67 abundance.
Circ_0005273 was increased in BC tissues and cells. Circ_0005273 knockdown might inhibit BC cell proliferation, migration, invasion, glutamine metabolism, and induce apoptosis. Circ_0005273 was a miR-509-3p, and the repression role of circ_0005273 absence on BC cell development was weakened by miR-509-3p inhibitor or HMMR overexpression. Circ_0005273 up-regulated the expression of HMMR by sponging miR-509-3p. Additionally, circ_0005273 silencing might hinder tumor growth in vivo.
Circ_0005273 knockdown might repress BC cell malignant behaviors by regulating the miR-509-3p/HMMR axis, which might provide a potential therapeutic target for BC.
乳腺癌（BC）是一种常见的恶性肿瘤，威胁着全球女性的健康。hsa_circ_0005273 已被确定为某些实体瘤（包括 BC）的致癌因素。然而，circ_0005273 在 BC 中的分子机制尚不清楚。
通过实时定量聚合酶链反应检测 BC 中 circ_0005273、miR-509-3p 和透明质酸介导的运动受体（HMMR）mRNA 的表达。通过 5-乙炔基-2'-脱氧尿苷、Transwell 和流式细胞术检测细胞增殖、迁移和侵袭以及细胞凋亡。通过特定试剂盒检测糖酵解水平。通过 Western blot 检测蛋白表达。还通过双荧光素酶报告、RNA 下拉和 RNA 免疫沉淀检测 miR-509-3p 与 circ_0005273 或 HMMR 之间的结合。使用异种移植肿瘤模型检测小鼠肿瘤变化，并用免疫组化检测 Ki-67 丰度。
circ_0005273 在 BC 组织和细胞中升高。circ_0005273 敲低可能抑制 BC 细胞增殖、迁移、侵袭、谷氨酰胺代谢并诱导细胞凋亡。circ_0005273 是 miR-509-3p 的一种，circ_0005273 缺失对 BC 细胞发育的抑制作用可被 miR-509-3p 抑制剂或 HMMR 过表达减弱。circ_0005273 通过海绵吸附 miR-509-3p 上调 HMMR 的表达。此外，circ_0005273 沉默可能会阻碍体内肿瘤生长。
circ_0005273 敲低可能通过调节 miR-509-3p/HMMR 轴抑制 BC 细胞恶性行为，为 BC 提供了一个潜在的治疗靶点。
