Hsa_circ_0001944 promotes colorectal cancer progression through the miR-665/IGF2BP1/PKM2 axis-mediated glycolysis

Colorectal cancer (CRC) is a highly heterogeneous malignancy with a poor prognosis. Although previous studies have suggested that circular RNA hsa_circ_0001944 is involved in CRC progression, its precise biological role remains unclear. This study aimed to investigate the function and underlying mechanism of hsa_circ_0001944 in CRC. Fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RT-qPCR) were used to assess the expression and subcellular localization of hsa_circ_0001944 in CRC tissues and cell lines. Functional assays, including Cell Counting Kit-8 (CCK-8), ethynyl-2'-deoxyuridine (EdU) incorporation, Transwell migration assays, and xenograft tumor models, were performed to evaluate its biological effects. Mechanistic investigations were conducted using bioinformatics analysis, dual-luciferase reporter assays, and rescue experiments. Cellular metabolism was assessed using Seahorse extracellular flux analysis to measure extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). The results showed that hsa_circ_0001944 was significantly upregulated in CRC tissues and cell lines. Knockdown of hsa_circ_0001944 significantly inhibited cell proliferation, migration, and tumor growth in vitro and in vivo. Mechanistically, hsa_circ_0001944 acted as a molecular sponge for miR-665, thereby regulating insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). Rescue experiments demonstrated that miR-665 inhibition or IGF2BP1 overexpression reversed the suppressive effects induced by hsa_circ_0001944 silencing. Furthermore, IGF2BP1 overexpression restored aerobic glycolysis, as evidenced by increased ECAR and decreased OCR, and regulated pyruvate kinase M2 (PKM2) expression. In conclusion, hsa_circ_0001944 promotes colorectal cancer progression by regulating the miR-665/IGF2BP1/PKM2 axis and metabolic reprogramming.