The present study aimed to investigate the influence of circular RNA nuclear receptor-interacting protein 1 (circNRIP1) on the chemotherapeutic effect of 5-fluorouracil (5-FU) in colorectal cancer (CRC) and reveal its potential molecular mechanisms. The effects of circNRIP1 on cell proliferation, migration and invasion, and apoptosis were evaluated using Cell Counting Kit-8, Transwell and flow cytometric assays, respectively. A dual-luciferase reporter assay was performed to verify the potential interaction between circNRIP1 and microRNA (miR)-532-3p. The results of the present study indicated that circNRIP1 was upregulated in CRC and its increased expression was associated with CRC progression. Furthermore, overexpression of circNRIP1 promoted CRC cell proliferation, invasion and migration, while it inhibited apoptosis. Knockdown of circNRIP1 significantly enhanced the 5-FU-induced inhibition of the viability of HCT116 and SW480 cells. Bioinformatics analysis predicted that miR-532-3p was a direct target of circNRIP1, which was further confirmed by a dual-luciferase reporter assay. miR-532-3p silencing reversed the effects of circNRIP1 knockdown on the sensitivity of 5-FU in the chemotherapy of CRC. The results suggested that circNRIP1 and miR-532-3p may be utilized to improve the diagnosis of CRC and serve as diagnostic markers. In conclusion, overexpression of circNRIP1 promoted the progression of CRC, while circNRIP1 silencing sensitized CRC cells to 5-FU via sponging miR-532-3p.

Purpose Dexmedetomidine (DEX) stabilizes intraoperative blood glucose levels and reduces insulin resistance (IR), a common perioperative complication. However, the molecular mechanisms underlying these effects remain unclear. Since endoplasmic reticulum stress (ERS) is a mechanism of IR, this study sought to examine whether DEX can effectively alleviate IR by reducing ERS. Methods HepG2 and LO2 cells were treated with different concentrations of insulin. The glucose content assay and Cell Counting Kit-8 (CCK-8) were then employed to determine the optimal insulin concentration capable of inducing IR without affecting cell viability. Insulin-resistant hepatocytes were cultured with different concentrations of DEX for 24 h, and the glucose concentration in the supernatant was measured. ERS was assessed by qPCR and western blotting. The latter was also used to quantify the expression of phosphorylated protein kinase B (p-AKT), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6 phosphatase (G6Pase), which are key proteins involved in the action of insulin. Results After 48-h of culturing with 10 μg/mL insulin, glucose consumption in hepatocytes was found to be reduced. IR hepatocytes cultured with 10, 100, or 1000 ng/ml DEX for 24 h showed a concentration-dependent increase in glucose consumption. Elevated mRNA and protein levels of ERS markers binding immunoglobulin protein (BIP) and ER protein 29 (ERp29), were reversed by DEX treatment. Moreover, reduced p-AKT and increased PEPCK and G6Pase protein levels in IR hepatocytes were also restored following DEX treatment. Conclusion DEX may alleviate IR in hepatocytes by reducing ERS serving to restore insulin action via the IRS-1/PI3K/AKT pathway.