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异丙酚通过 miR-145-5p/TOP2A 轴调节膀胱癌细胞的增殖、侵袭和迁移。

Propofol modulates the proliferation, invasion and migration of bladder cancer cells through the miR‑145‑5p/TOP2A axis.

机构信息

Department of Anesthesiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China.

出版信息

Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12078. Epub 2021 Apr 13.

DOI:10.3892/mmr.2021.12078
PMID:33846791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8060790/
Abstract

Propofol‑based anesthesia has been reported to reduce the recurrence and metastasis of a number of cancer types following surgical resection. However, the effects of propofol in bladder cancer (BC) are yet to be fully elucidated. The aim of the present study was to investigate the functions of propofol in BC and their underlying mechanisms. In the study, the expression of microRNA (miR)‑145‑5p in BC tissues and cell lines was evaluated using reverse transcription‑quantitative PCR, and the effects of propofol on BC cells were determined using cell viability, wound healing and Transwell cell invasion assays, bioinformatics analysis, western blotting, immunohistochemistry and tumor xenograft models. It was found that propofol significantly suppressed the proliferation, migration and invasion of BC cells . In addition, propofol induced miR‑145‑5p expression in a time‑dependent manner, and miR‑145‑5p knockdown attenuated the inhibitory effects of propofol on the proliferation, migration and invasion of BC cells. Topoisomerase II α (TOP2A) was a direct target of miR‑145‑5p, and silencing TOP2A reversed the effects of miR‑145‑5p knockdown in propofol‑treated cells. Furthermore, propofol suppressed tumor xenograft growth, which was partially attenuated by miR‑145‑5p knockdown. The present study provided novel insight into the advantages of surgical intervention with propofol anesthesia in patients with BC.

摘要

基于异丙酚的麻醉已被报道可降低多种癌症类型在手术切除后的复发和转移。然而,异丙酚在膀胱癌(BC)中的作用尚未完全阐明。本研究旨在探讨异丙酚在 BC 中的作用及其潜在机制。在研究中,采用逆转录定量 PCR 评估 BC 组织和细胞系中 microRNA(miR)-145-5p 的表达,并通过细胞活力测定、划痕愈合和 Transwell 细胞侵袭试验、生物信息学分析、western blot 分析、免疫组化和肿瘤异种移植模型来确定异丙酚对 BC 细胞的影响。结果发现,异丙酚显著抑制 BC 细胞的增殖、迁移和侵袭。此外,异丙酚呈时间依赖性诱导 miR-145-5p 表达,miR-145-5p 敲低减弱了异丙酚对 BC 细胞增殖、迁移和侵袭的抑制作用。拓扑异构酶 IIα(TOP2A)是 miR-145-5p 的直接靶标,沉默 TOP2A 逆转了 miR-145-5p 敲低对异丙酚处理细胞的影响。此外,异丙酚抑制肿瘤异种移植生长,miR-145-5p 敲低部分减弱了这种抑制作用。本研究为 BC 患者接受异丙酚麻醉手术干预的优势提供了新的见解。

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