Long non‑coding RNA MIAT knockdown potentiates the therapeutic effect of transcatheter arterial embolization in liver cancer by regulating the miR‑203a/HIF‑1α axis

Liu,Jian; Cao,Guangshao; Liu,Jianwen; Zhao,Xiaoyang; Cao,Huicun

doi:10.3892/or.2020.7618

Long non‑coding RNA MIAT knockdown potentiates the therapeutic effect of transcatheter arterial embolization in liver cancer by regulating the miR‑203a/HIF‑1α axis

Authors:
- Jian Liu
- Guangshao Cao
- Jianwen Liu
- Xiaoyang Zhao
- Huicun Cao
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Affiliations: Department of Intervention, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China
Published online on: May 21, 2020 https://doi.org/10.3892/or.2020.7618
Pages: 722-734

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Abstract

Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) are often used for palliative treatment of liver cancer. TAE and TACE can induce severe hypoxia. The present study investigated the effect of the myocardial infarction associated transcript (MIAT)/microRNA (miR)‑203a/hypoxia‑inducible factor 1‑α (HIF‑1α) axis on the therapeutic activity of TAE for liver cancer using hypoxia‑treated liver cancer cells and rat orthotopic liver tumors. MIAT, miR‑203a and HIF‑1α mRNA levels were assessed by reverse transcription‑quantitative PCR assay. The protein expression of HIF‑1α, Ki‑67 and vascular endothelial growth factor was determined by western blot assay. The proliferative, migratory and invasive potential of cells was assessed by CCK‑8, Transwell migration and invasion assays, respectively. The association between MIAT, miR‑203a and HIF‑1α was investigated through bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation and RNA pull‑down assay. In vivo experiments were performed to explore the effect of TAE alone or in combination with MIAT knockdown on the growth of rat liver tumors. The results revealed that MIAT and HIF‑1α were highly expressed, and miR‑203a was lowly expressed in liver tumors of patients with liver cancer after TACE treatment and hypoxia‑stimulated liver cancer cells. MIAT sequestered miR‑203a from its target HIF‑1α. MIAT knockdown, miR‑203a overexpression or HIF‑1α loss inhibited proliferation, migration and invasion in hypoxia‑treated liver cancer cells. MIAT knockdown enhanced TAE‑mediated antitumor effects by upregulating miR‑203a and downregulating HIF‑1α in rat liver tumors. In conclusion, MIAT knockdown potentiated the therapeutic effect of TAE in liver cancer by regulating the miR‑203a/HIF‑1α axis in vitro and in vivo, thus expanding our understanding on the function and molecular basis of MIAT in TAE treatment for liver cancer.

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