期刊
CANCER MANAGEMENT AND RESEARCH
卷 12, 期 -, 页码 6795-6806出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S251952
关键词
colorectal cancer; circ_0136666; miR-383; CREB1; proliferation; apoptosis; glycolysis
类别
Background: The changes in dietary patterns cause an increased incidence of colorectal cancer (CRC) globally. We aimed to explore the mechanism behind circular RNA circ_0136666 in the progression of CRC. Materials and Methods: The expression of circ_0136666, miR-383 and cAMP response element binding protein 1 (CREB1) was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis and glycolysis were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry and glucose or lactate detection kit, respectively. The combination between miR-383 and circ_0136666 or CREB1 in 293T cells was predicted by Circular RNA Interactome or Starbase software and confirmed by dual-luciferase reporter assay. Western blot assay was performed to detect the abundance of CREB1, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA) in CRC cells. Murine xenograft model was established to verify the function of circ_0136666 in vivo. Results: circ_0136666 was aberrantly up-regulated in CRC tissues and cells, and it promoted the proliferation and glycolysis and inhibited the apoptosis of CRC cells. circ_0136666 accelerated the progression of CRC through directly targeting and down-regulating miR-383. CREB1 could bind to miR-383 in 293T cells. The overexpression of CREB1 reversed the inhibitory effects of miR-383 accumulation on the proliferation and glycolysis and the promoting impact on the apoptosis of CRC cells. The enrichment of CREB1 was modulated by circ_0136666/miR-383 signaling in CRC cells. The glycolysis-related proteins (HK2 and LDHA) were modulated by circ_0136666/miR-383/CREB1 axis in CRC cells. circ_0136666 accelerated the growth of CRC tumors via circ_0136666/miR-383/CREB1 axis in vivo. Conclusion: circ_0136666 deteriorated CRC through miR-383/CREB1 axis. circ_0136666/ miR-383/CREB1 axis might be an underlying therapeutic target for CRC therapy.
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