Department of Colorectal Anorectal Surgery, Shanxi Provincial Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030000, Shanxi Province, China.
The Second Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi Province, China.
Biochem Genet. 2023 Jun;61(3):1210-1229. doi: 10.1007/s10528-022-10316-2. Epub 2022 Dec 21.
The aim of this study was to investigate the role of circRNA insulin growth factor 1 receptor (circ-IGF1R) in colorectal cancer (CRC). Glycolytic metabolism was analyzed by glucose uptake and lactate production using the corresponding kits. The protein levels were determined using Western blot. The effect of circ-IGF1R on CRC in vivo was explored by xenograft experiment in mice. Circ-IGF1R was up-regulated in CRC tissues and cells. Knockdown of circ-IGF1R inhibited proliferation, migration, invasion and glycolysis but induced apoptosis of CRC cells. Circ-IGF1R interacted with miR-362-5p and miR-362-5p inhibitor attenuated the anti-tumor effects of circ-IGF1R downregulation on CRC cells. HMGB3 acted as a downstream target for miR-362-5p, and circ-IGF1R facilitated the malignant behaviors of CRC cells by regulating HMGB3. Circ-IGF1R activated the Wnt/β-catenin pathway via targeting miR-362-5p/HMGB3 axis. Tumor growth in vivo was reduced after knockdown of circ-IGF1R. Circ-IGF1R might be a novel biomolecular target for CRC diagnosis and treatment.
本研究旨在探讨环状 RNA 胰岛素样生长因子 1 受体(circ-IGF1R)在结直肠癌(CRC)中的作用。通过相应的试剂盒分析葡萄糖摄取和乳酸生成来检测糖酵解代谢。使用 Western blot 测定蛋白水平。通过在小鼠中的异种移植实验来探索 circ-IGF1R 对 CRC 的体内作用。CRC 组织和细胞中 circ-IGF1R 上调。circ-IGF1R 的敲低抑制 CRC 细胞的增殖、迁移、侵袭和糖酵解,但诱导其凋亡。circ-IGF1R 与 miR-362-5p 相互作用,miR-362-5p 抑制剂减弱了 circ-IGF1R 下调对 CRC 细胞的抗肿瘤作用。HMGB3 是 miR-362-5p 的下游靶标,circ-IGF1R 通过调控 HMGB3 促进 CRC 细胞的恶性行为。circ-IGF1R 通过靶向 miR-362-5p/HMGB3 轴激活 Wnt/β-catenin 通路。circ-IGF1R 的敲低后体内肿瘤生长减少。circ-IGF1R 可能是 CRC 诊断和治疗的新的生物分子靶标。