Propofol Inhibits Thyroid Cancer Cell Proliferation, Migration, and Invasion by Suppressing SHH and PI3K/AKT Signaling Pathways via the miR-141-3p/BRD4 Axis

Abstract

Objective. This study explores the effect and mechanism of propofol for thyroid tumor. Methods. Culture human normal thyroid cells Nthy-ori 3-1 and thyroid cancer cell line TPC-1. TPC-1 cells were divided into the propofol group (treated with propofol), miR-141-3p group (transfected with the miR-141-3p mimic), negative control group (transfected with miR-NC), miR-141-3p + pcDNA-BRD4 group (transfected with the miR-141-3p mimic and pcDNA-BRD4), miR-141-3p + pcDNA group (transfected with the miR-141-3p mimic and pcDNA), siBRD4 group (transfected with siBRD4), and si-control group (transfected with si-control). The detection of miR-141-3p and BRD4 expression in cells was done by RT-qPCR, and the dual-luciferase reporter gene method and western blotting were used to verify the targeting relationship between miR-141-3p and BRD4. MTT method was used to test cell proliferation, transwell method was used to test cell migration and invasion, and western blotting was used to test SHH, GLI1, p-PI3K, and p-AKT protein expression. Results. Compared with Nthy-ori 3-1 cells, the expression of miR-141-3p in TPC-1 cells was markedly decreased. Propofol treatment and excessive expression of miR-141-3p could influence the phenotype of TPC-1 cells. BRD4 is one of the target genes of miR-141-3p, and its expression is negatively regulated by miR-141-3p. Overexpression of BRD4 can partially reverse the restraining effect of miR-141-3p on the TPC-1 cell phenotype. Both miR-141-3p and BRD4 can regulate the activity of SHH and PI3K/AKT signaling pathways. Conclusion. Propofol can inhibit the activity of SHH and PI3K/AKT pathways by targeting downregulating BRD4 through miR-141-3p, thereby inhibiting the phenotype of TPC-1 cells.

MicroRNA-196-5p targets Derlin-1 to induce autophagy in human osteosarcoma cells

“…6). These findings are consistent with our earlier demonstration about the results of the luciferase reporter assay and the published results on pcDNA (Zhang et al, 2021). The molecular basis of the antiproliferative effects of miR-196-5p overexpression that mediates through the decrease in the expression of Derlin-1 in Saos2 osteosarcoma cells remains unclear and needs further investigation.…”

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

“… 254 There is also evidence suggesting negative regulation of BRD4 by miR-141-3p. 255 In ovarian cancer, SET7 has been shown to be modulated by miR-153, and lncRNA SNHG6 has been found to downregulate SETD7 by posttranscriptional destabilization. 256 …”

The effect of propofol on chemosensitivity of paclitaxel in cervical cancer cells

“…Propofol‐induced anesthesia usually occurs at a blood concentration of 4–6 mg/L, which is equivalent to 22–34 μM 2 . Accumulating research has demonstrated that propofol can suppress the malignant biological behaviors of various cancer cells via many signaling pathways 3,4 . In addition, numerous studies have demonstrated that propofol reduces the resistance of cancer cells to many chemotherapeutic drugs 5,6 .…”

“… 2 Accumulating research has demonstrated that propofol can suppress the malignant biological behaviors of various cancer cells via many signaling pathways. 3 , 4 In addition, numerous studies have demonstrated that propofol reduces the resistance of cancer cells to many chemotherapeutic drugs. 5 , 6 For instance, propofol could increase the cytotoxicity of cisplatin in liver cancer.…”