Propofol suppresses lung cancer tumorigenesis by modulating the circ‐ERBB2/miR‐7‐5p/FOXM1 axis

Abstract

Background Propofol is a commonly used anesthetic for cancer surgery. Previous studies have shown that propofol has an anticancer role in various cancers, including lung cancer. This study aimed to investigate the role of propofol in lung cancer and its underlying mechanism. Methods Cell proliferation was determined by cell counting kit‐8 (CCK‐8) and colony formation assays. Flow cytometry and transwell assays were used to detect cell apoptosis and invasion, respectively. Glycolysis was evaluated by detecting glucose consumption, lactate production and ATP/ADP ratios. The levels of circular RNA erb‐b2 receptor tyrosine kinase 2 (circ‐ERBB2), microRNA‐7‐5p (miR‐7‐5p) and forkhead box M1 (FOXM1) were tested by quantitative real‐time PCR and Western blot. The binding relationship between miR‐7‐5p and circ‐ERBB2/FOXM1 was verified by dual‐luciferase reporter assay. Moreover, in vivo experiments were performed by establishing a mouse xenograft model. Results Propofol suppressed cell proliferation, invasion and glycolysis and expedited apoptosis in lung cancer cells. Circ‐ERBB2 and FOXM1 were upregulated, while miR‐7‐5p was decreased in lung cancer tissues and cells. Propofol suppressed lung cancer cell progression by regulating circ‐ERBB2. Additionally, miR‐7‐5p directly interacted with circ‐ERBB2 and FOXM1. Also, propofol played an antitumor role in lung cancer via modulating miR‐7‐5p or FOXM1. Moreover, circ‐ERBB2 knockdown enhanced the suppressive effect of propofol on tumor growth in vivo. Conclusions Propofol inhibited lung cancer progression via mediating circ‐ERBB2/miR‐7‐5p/FOXM1 axis, which might provide an effective therapeutic target for lung cancer therapy.

Circ‐ERBB2 knockdown sensitized colorectal cancer cells to 5‐FU via miR‐181a‐5p/PTEN/Akt pathway

“…[22] Previous studies have found that circ-ERBB2 inhibiting circ-ERBB2 expression. [21] In this study, we predicted and confirmed miR-181a-5p as a target for circ-ERBB2. Consistent with previous studies, we found that low miR-181a-5p expression in CRC, and overexpression of miR-181a-5p attenuates the malignancy of CRC cells.…”

“…Circ-ERBB2 has been previously suggested to be related to prognosis and malignancy of a variety of tumors. [18][19][20][21] A study revealed that circ-ERBB2 is an important regulator of cancer cell proliferation, which can serve as the novel target in anti-gallbladder cancer treatment. [18] In gastric cancer, circ-ERBB2 was also found to be a potential prognostic biomarker.…”

Propofol mediates miR-199a/PAK4 axis to regulate the proliferation, invasion and migration of non-small cell lung carcinoma cells

“…Cells in logarithmic growth phase (approximately the 3rd-5th generation) were used for subsequent experiments. H1299 and A549 cells were treated with 0, 5 and 10 µg/mL propofol (Sigma-Aldrich Chemical Co.) which was dissolved in dimethyl sulfoxide (DMSO, Solarbio) (Gao et al 2021), and miR-199a expression was determined at 12, 24, and 48 h, respectively.…”

Propofol Regulates ER Stress to Inhibit Tumour Growth and Sensitize Osteosarcoma to Doxorubicin

“…Molecular mechanisms regarding the role of propofol on cancer have been proposed. For example, propofol has been reported to suppress lung cancer tumorigenesis by modulating the circ-ERBB2/miR-7-5p/FOXM1 axis [ 14 ]. Other studies showed that propofol suppressed colorectal cancer development by the circ-PABPN1/miR-638/SRSF1 axis [ 15 ] and mediated pancreatic cancer cell activity through the repression of ADAM8 via SP1 [ 16 , 17 ].…”