B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway

Liao,Haixiu; Ding,Meng; Zhou,Nannan; Yang,Ying; Chen,Liwen

doi:10.3892/mmr.2022.12595

B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway

Authors:
- Haixiu Liao
- Meng Ding
- Nannan Zhou
- Ying Yang
- Liwen Chen
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Affiliations: Department of Laboratory Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
Published online on: January 11, 2022 https://doi.org/10.3892/mmr.2022.12595
Article Number: 79
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial‑mesenchymal transition (EMT) is a key step in cancer metastasis. B7‑H3, a co‑signaling molecule associated with poor prognosis of non‑small cell lung cancer (NSCLC), promotes the metastasis of NSCLC by activating the EMT process. However, its underlying mechanism remains poorly understood. In the present study, it was shown that CRISPR/Cas9‑mediated B7‑H3 deletion downregulated the expression of the class III histone deacetylase, sirtuin‑1 (SIRT1), in NSCLC A549 cells. Accordingly, SIRT1 silencing resulted in markedly decreased migration and invasion of A549 cells. Both B7‑H3 gene‑edited and SIRT1‑silenced cells were typically characterized by an increased expression of the epithelial marker E‑cadherin, and downregulation of the mesenchymal markers N‑cadherin and vimentin, as compared with mock‑edited and scrambled negative small interfering RNA control, respectively. It was further demonstrated that B7‑H3 ablation significantly downregulated phosphorylated AKT/protein kinase B expression, and SIRT1 expression was substantially suppressed by the PI3K‑specific inhibitor, LY294002. Taken together, the findings of the present study revealed that B7‑H3‑induced signaling upregulates SIRT1 expression via the PI3K/AKT pathway to promote EMT activation that is associated with metastasis in NSCLC.

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