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Promotes Lung Adenocarcinoma Malignancy by Activating transcription via Histone H1 Displacement.

Balkan medical journal 2026 Vol.43(4) p. 183-95

Huang G, Gao L, Fang S, Xu L, Zhao X

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[BACKGROUND] Epithelial–mesenchymal transition and cancer cell stemness (CSC) are critical processes that driving the invasion and lethality of lung adenocarcinoma (LUAD).

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APA Huang G, Gao L, et al. (2026). Promotes Lung Adenocarcinoma Malignancy by Activating transcription via Histone H1 Displacement.. Balkan medical journal, 43(4), 183-95. https://doi.org/10.4274/balkanmedj.galenos.2026.2025-10-260
MLA Huang G, et al.. " Promotes Lung Adenocarcinoma Malignancy by Activating transcription via Histone H1 Displacement.." Balkan medical journal, vol. 43, no. 4, 2026, pp. 183-95.
PMID 41777148

Abstract

[BACKGROUND] Epithelial–mesenchymal transition and cancer cell stemness (CSC) are critical processes that driving the invasion and lethality of lung adenocarcinoma (LUAD). The chromatin remodeler has been implicated in other cancers; however, its specific role and underlying mechanism in LUAD progression remain unclear.

[AIMS] To elucidate the function of in LUAD.

[STUDY DESIGN] This study integrated bioinformatics analysis, cellular functional assays, and in vivo orthotopic lung cancer models to investigate the oncogenic role of .

[METHODS] expression and its correlation with patient prognosis were analyzed using public databases. was silenced using two independent short hairpin RNAs in A549 and H1650 LUAD cell lines, and subsequent changes in invasion, migration, and stemness markers were assessed. Tumor metastasis was evaluated using orthotopic and tail-vein injection mouse models. The regulatory mechanism by which controls expression was investigated using dual-luciferase reporter and chromatin immunoprecipitation assays.

[RESULTS] was significantly upregulated in LUAD and was associated with poor patient prognosis. Silencing in LUAD cells significantly reduced their invasion and migration capabilities (adj. < 0.01). Furthermore, knockdown resulted in downregulation of SNAIL, upregulation of E-cadherin, and impairment of stem-like characteristics, as demonstrated by decreased CSC marker expression and reduced sphere-forming ability (adj. < 0.05). In the orthotopic model, deficiency markedly inhibited tumor metastasis (adj. < 0.001). Mechanistically, transcriptionally activated (adj. < 0.01). Furthermore, knockdown increased histone H1 occupancy at the promoter (adj. < 0.01), indicating that facilitates an open chromatin state. Rescue experiments further confirmed that is required for -mediated maintenance of tumor invasiveness and cancer stemness.

[CONCLUSION] promotes LUAD malignancy by transcriptionally activating , thereby driving EMT and cancer stemness.

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