miR‑425 regulates lipophagy via SIRT1 to promote sorafenib resistance in liver cancer

Sun,Gongping; Yang,Liang; Wei,Shibo; Jin,Hongyuan; Li,Bowen; Li,Hangyu

doi:10.3892/ol.2021.12956

miR‑425 regulates lipophagy via SIRT1 to promote sorafenib resistance in liver cancer

Authors:
- Gongping Sun
- Liang Yang
- Shibo Wei
- Hongyuan Jin
- Bowen Li
- Hangyu Li
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Affiliations: Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning 110032, P.R. China
Published online on: August 2, 2021 https://doi.org/10.3892/ol.2021.12956
Article Number: 695
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is one of the most malignant cancer, with poor outcomes and a high incidence rate, and current treatment approaches to prevent tumor progression and development remain unsatisfactory. Therefore, it is urgent to explore novel methods to inhibit tumor growth and metastasis. Autophagy is a highly conserved process associated with metastasis and drug resistance. Lipids are selectively recognized and degraded via autophagy; thus, autophagy is a crucial process to maintain tumor self‑protection. MicroRNA (miR)‑425 is a tumor‑associated gene involved in liver cancer development that can induce cell proliferation and drug resistance. Using Cell Counting Kit‑8 assays, western blot analysis and immunofluorescence assays, the present study revealed that inhibition of miR‑425 promoted lipophagy by mediating the autophagy process, which in turn helps to promote sorafenib resistance. Using a bioinformatics website, it was revealed that autophagy promoted lipophagy by targeting silent information regulator 2 homolog 1 (SIRT1). The results of luciferase reporter assays supported this finding, and rescue experiments provided additional evidence. Overall, the current results suggested that inhibition of miR‑425 expression increased SIRT1 expression to promote lipophagy, leading to the inhibition of liver cancer cell proliferation.

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