Propofol‑induced HOXA11‑AS promotes proliferation, migration and invasion, but inhibits apoptosis in hepatocellular carcinoma cells by targeting miR‑4458

丙泊酚诱导的 HOXA11-AS 促进增殖、迁移和侵袭,但通过靶向 miR-4458 抑制肝细胞癌细胞凋亡

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作者:Furong Song, Jun Liu, Yawei Feng, Yi Jin

Abstract

Propofol is a commonly used drug for the induction and maintenance of anesthesia. Previous studies have reported that propofol is involved in the progression of numerous human cancer types, including hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms in HCC are yet to be elucidated. The present study aimed to investigate the potential mechanism of propofol in HCC development. MTT assay, flow cytometry analysis and Transwell assays were conducted to examine cell proliferation, apoptosis, migration and invasion, respectively. Western blotting was also performed to determine the protein expression levels of Bcl‑2 and cleaved‑caspase 3. An in vivo experiment was performed to assess the effect of propofol on tumor growth. Moreover, reverse transcription‑quantitative PCR was conducted to measure the mRNA expression levels of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11‑AS) and microRNA (miR)‑4458. Dual‑luciferase reporter and RNA pull‑down assays were performed to evaluate the target relationship between HOXA11‑AS and miR‑4458. It was demonstrated that propofol inhibited HCC cell proliferation, migration and invasion, and promoted cell apoptosis in vitro. Furthermore, propofol could suppress tumor growth in vivo. Propofol suppressed the expression of HOXA11‑AS in HCC cells, while HOXA11‑AS overexpression reversed the inhibitory effect of propofol treatment on cell progression in HCC. In addition, miR‑4458 was identified as a target of HOXA11‑AS, and miR‑4458 inhibition reversed the effect of HOXA11‑AS knockdown on HCC cell progression. The results also indicated that propofol promoted the expression of miR‑4458, while HOXA11‑AS restored this effect in HCC. Thus, it was suggested that propofol suppressed cell progression by modulating the HOXA11‑AS/miR‑4458 axis in HCC.

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