Gastroenterology Department, The Number Two Hospital of Shanxi Medical University, Taiyuan, China.
Department of Hematology, The Number Two Hospital of Shanxi Medical University, Taiyuan, China.
J Clin Lab Anal. 2022 Sep;36(9):e24641. doi: 10.1002/jcla.24641. Epub 2022 Aug 10.
Circular RNAs (circRNAs) have been confirmed to be key regulators for colorectal cancer (CRC) progression. The purpose of this research was to explore the biological role and mechanism of hsa_circ_0045932 in CRC.
RT-qPCR and Western blot (WB) were applied to examine RNA and protein levels, respectively. MTT assay, EdU assay, and transwell assay were used to detect cell proliferative, migration, and invasion. Glucose uptake and lactic acid level were determined to assess cellular glycolysis. Dual-luciferase reporter and RIP assays were carried out to detect the relationship between miR-873-5p and hsa_circ_0045932 or hexokinase 2 (HK2). Xenograft mice model was established to confirm the function of hsa_circ_0045932 in vivo.
Hsa_circ_0045932 was overexpressed in CRC tissue samples and cells. Hsa_circ_0045932 knockdown repressed CRC cell proliferation, invasion, migration, and glycolysis abilities in vitro. MiR-873-5p could be sponged by hsa_circ_0045932, and its inhibitor also reversed the inhibitory effect of hsa_circ_0045932 knockdown on CRC cell progression. HK2 was targeted by miR-873-5p, and hsa_circ_0045932 regulated HK2 expression through targeting miR-873-5p. Overexpression of HK2 reversed the repressive effect of hsa_circ_0045932 knockdown on CRC cell malignant behaviors. Furthermore, the pro-tumor role of hsa_circ_0045932 in vivo was also confirmed using animal experiments.
Hsa_circ_0045932 promoted CRC progression through sponging miR-873-5p to up-regulate HK2, which might offer novel therapeutic target for CRC clinical intervention.
环状 RNA（circRNAs）已被证实为结直肠癌（CRC）进展的关键调节因子。本研究旨在探讨 hsa_circ_0045932 在 CRC 中的生物学作用和机制。
应用 RT-qPCR 和 Western blot（WB）分别检测 RNA 和蛋白水平。MTT 检测、EdU 检测和 Transwell 检测用于检测细胞增殖、迁移和侵袭。葡萄糖摄取和乳酸水平测定用于评估细胞糖酵解。双荧光素酶报告和 RIP 实验用于检测 miR-873-5p 与 hsa_circ_0045932 或己糖激酶 2（HK2）的关系。建立异种移植小鼠模型以体内验证 hsa_circ_0045932 的功能。
hsa_circ_0045932 在 CRC 组织样本和细胞中高表达。hsa_circ_0045932 敲低抑制 CRC 细胞体外增殖、侵袭、迁移和糖酵解能力。miR-873-5p 可被 hsa_circ_0045932 海绵吸附，其抑制剂也可逆转 hsa_circ_0045932 敲低对 CRC 细胞进展的抑制作用。HK2 是 miR-873-5p 的靶点，hsa_circ_0045932 通过靶向 miR-873-5p 调节 HK2 表达。HK2 的过表达逆转了 hsa_circ_0045932 敲低对 CRC 细胞恶性行为的抑制作用。此外，动物实验也证实了 hsa_circ_0045932 在体内的促肿瘤作用。
hsa_circ_0045932 通过海绵吸附 miR-873-5p 上调 HK2 促进 CRC 进展，这可能为 CRC 临床干预提供新的治疗靶点。
