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异丙酚诱导的 miR-125a-5p 通过抑制 LIN28B 抑制卵巢癌细胞的增殖和转移。

Propofol‑induced miR‑125a‑5p inhibits the proliferation and metastasis of ovarian cancer by suppressing LIN28B.

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.

Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, P.R. China.

出版信息

Mol Med Rep. 2020 Aug;22(2):1507-1517. doi: 10.3892/mmr.2020.11223. Epub 2020 Jun 11.

Abstract

Propofol, a commonly used intravenous anesthetic agent during surgery, has relatively widespread pharmacological actions. Previous studies have reported that propofol may act as an antitumor drug in several cancer types, such as pancreatic cancer, lung cancer and gastric cancer. However, the underlying mechanism in ovarian cancer remain unknown. Therefore, the present study investigated the pharmacological effect of propofol on microRNAs (miRNAs) in ovarian cancer treatment. Propofol (1, 5 or 10 µg/ml) was used to treat A2780 and SKOV3 ovarian cancer cells for 1, 2, 3, 4 or 5 days. The MTT assay was used to detect cell viability, while wound healing and Transwell assays were utilized to assess the invasive and migratory abilities. The bioinformatics prediction approach identified differentially expressed miRNAs (miRs) that were used in Gene Ontology, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes analyses. The expression levels of miR‑125a‑5p and lin‑28 homolog B (LIN28B) were evaluated by reverse transcription‑quantitative PCR (RT‑qPCR). A luciferase assay was performed to identify the relationship between miR‑125a‑5p and LIN28B. Western blotting was conducted to measure the protein expression of LIN28B. It was demonstrated that propofol significantly upregulated miR‑125a‑5p to exert its antitumor activity. RT‑qPCR results suggested that propofol could upregulate miR‑125a‑5p and LIN28B expression levels in ovarian cancer cell lines. Western blot analysis also indicated that propofol could enhance the expression of LIN28B in ovarian cancer cell lines. The luciferase assay identified that miR‑125a‑5p could directly inhibit the expression of LIN28B to suppress proliferation and metastasis in ovarian cancer. In conclusion, these results suggested that propofol inhibited ovarian cancer proliferation and metastasis by enhancing miR‑125a‑5p, which targets LIN28B.

摘要

丙泊酚是一种常用于手术的静脉麻醉剂,具有相对广泛的药理学作用。先前的研究表明,丙泊酚在几种癌症类型中可能具有抗肿瘤作用,如胰腺癌、肺癌和胃癌。然而,其在卵巢癌中的作用机制尚不清楚。因此,本研究探讨了丙泊酚在卵巢癌治疗中对 microRNAs(miRNAs)的药理学作用。将丙泊酚(1、5 或 10μg/ml)用于治疗 A2780 和 SKOV3 卵巢癌细胞 1、2、3、4 或 5 天。采用 MTT 法检测细胞活力,划痕愈合和 Transwell 实验检测侵袭和迁移能力。生物信息学预测方法鉴定差异表达的 miRNAs(miRs),并进行基因本体论、基因集富集分析和京都基因与基因组百科全书分析。采用逆转录-定量 PCR(RT-qPCR)评估 miR-125a-5p 和 lin-28 同源物 B(LIN28B)的表达水平。进行荧光素酶实验鉴定 miR-125a-5p 和 LIN28B 之间的关系。采用 Western blot 检测 LIN28B 蛋白表达。结果表明,丙泊酚可显著上调 miR-125a-5p 发挥其抗肿瘤活性。RT-qPCR 结果表明,丙泊酚可上调卵巢癌细胞系中 miR-125a-5p 和 LIN28B 的表达水平。Western blot 分析还表明,丙泊酚可增强卵巢癌细胞系中 LIN28B 的表达。荧光素酶实验鉴定 miR-125a-5p 可直接抑制 LIN28B 的表达,从而抑制卵巢癌细胞的增殖和转移。综上所述,这些结果表明,丙泊酚通过增强靶向 LIN28B 的 miR-125a-5p 抑制卵巢癌细胞增殖和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff39/7346589/96f5f3500fd4/MMR-22-02-1507-g00.jpg

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