Demethylation of <em>HACE1</em> gene promoter by propofol promotes autophagy of human A549&nbsp;cells

Li,Shanshan; Yang,Hui; Zhao,Min; Gong,Linli; Wang,Yahong; Lv,Zhiyong; Quan,Yuhang; Wang,Zhonghui

doi:10.3892/ol.2020.12143

Demethylation of HACE1 gene promoter by propofol promotes autophagy of human A549 cells

Authors:
- Shanshan Li
- Hui Yang
- Min Zhao
- Linli Gong
- Yahong Wang
- Zhiyong Lv
- Yuhang Quan
- Zhonghui Wang
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Affiliations: Department of Anesthesiology, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan 650118, P.R. China
Published online on: September 23, 2020 https://doi.org/10.3892/ol.2020.12143
Article Number: 280
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Propofol (2,6‑diisopropylphenol) is one of the most commonly used intravenous anesthetics and possesses a number of non‑anesthetic effects, including antitumor function. The aim of the present study was to elucidate the antitumor molecular mechanism of propofol on A549 and H1299 cells. A549 and H1299 cells were treated in the presence or absence of different concentrations (0, 60 or 120 µmol) of propofol for different durations (0, 24, 48 or 72 h), and proliferation was detected by MTT and colony formation assays; the protein levels of optineurin (OPTN) ubiquitination, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), methyl‑CpG binding domain protein 3 (MBD3) and Microtubule‑associated protein 1A/1B‑light chain 3 were detected by immunoblotting or quantitative (q)PCR; the methylation state of the HACE1 gene promoter was detected by bisulfite DNA sequencing; and binding of MBD3 on HACE1 gene promoter was detected by chromatin immunoprecipitation‑qPCR. Propofol inhibited proliferation of A549 and H1299 cells and promoted HACE1‑OPTN axis‑mediated selective autophagy activity by increasing the protein expression levels of HACE1 via demethylating its promoter region. Furthermore, propofol promoted expression levels of MBD3 and binding to the ‑1,000 to ‑1 bp (transcription start site) region of HACE1 gene promoter. MBD3‑knockdown experiments indicated that propofol inhibited proliferation of A549 cells in a MBD3‑dependent manner. Thus, the findings of the present study provided a potential antitumor molecular mechanism mediated by propofol.

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