Objective: This study aims to investigate the role of NAC1/HMGB1 signaling pathway in the epithelial-mesenchymal transition (EMT), invasion, and metastasis of lung cancer cell line.

Methods: Human lung cancer cell line A549 was used in this study. They were randomly divided into normal control group, sh-NAC1 empty vector group (sh-NAC1 NC), expression empty vector group (NAC1 NC), NAC1-shRNA and NAC1 over-expression group (NAC1). NAC1 and HMGB1 expression levels were detected by qRT-PCR method. Cell proliferation was detected by CCK8 kit. Cell cycles were detected by flow cytometry method. Cell invasion was detected by Transwell method. The expression levels of E-cadherin, N-cadherin, NAC1, and HMGB1 were detected by qRT-PCR and Western blotting methods.

Results: Compared with the control group, the expression level of NAC1 and cell proliferation in NAC1-shRNA group decreased, cells in G1 phase increased and cells in S phase decreased. In NAC1-shRNA group, E-cadherin expression levels increased and the expression levels of N-cadherin, HMGB1 and Vimentin decreased. In NAC1 group, the expression level of NAC1 and cell proliferation increased, cells in S phase increased and cells in G1 phase decreased, E-cadherin expression levels decreased and the expression levels of N-cadherin, HMGB1 and Vimentin increased. All these differences are statistically significant.

Conclusions: The expression of NAC1 and HMGB1 in lung cancer cells may affect the occurrence of EMT, the NAC1/ HMGB1 signaling pathway is associated with the EMT, invasion, and metastasis of lung cancer cells.

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