HDCA6 suppresses GATA6 expression to enhance cellular growth and migration in lung squamous cell carcinoma

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-03 DOI:10.1016/j.bbadis.2025.167757

Changhua Huang , Hua Yang , Hailong Wang , Shouyin Sheng , Limin Chen

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引用次数: 0

Abstract

Background

Lung squamous cell carcinoma (LUSC) exhibits a significant mortality rate and lacks effective targeted therapies. The GATA-binding factor 6 (GATA6), a pivotal regulator of lung development, undergoes reduced expression in LUSC and correlates with its metastasis and prognosis. However, the regulatory mechanisms underlying the down-regulation of GATA6 in LUSC remain elusive. HDAC6 emerges as a promising therapeutic target in preclinical cancer models. Nevertheless, its role in LUSC progression remains unexplored. Furthermore, the regulatory impact of HDAC6 on GATA6 expression needs clarification. The purpose of this work is to investigate HDAC6's involvement and regulatory mechanisms on the expression of GATA6 in LUSC.

Methods

The impacts of HDCA6 on the expression of GATA6 were assessed using qPCR, Western blot and CHIP assays. The tumorigenic capacity of HDAC6 in promoting the growth and migration of LUSC cell were determined through CCK8, EdU incorporation, Transwell, and xenograft tumor models. Immunohistochemistry assays were employed to detected expression of HDAC6 in tissue microarray of LUSC.

Results

A pan-HDACs inhibitor Trichostatin A and an HDAC6-specific inhibitor CAY10603 up-regulate the expression of GATA6, whereas HDAC6 overexpression down-regulates GATA6 level. Overexpression of HDAC6 promotes cell proliferation and migration in LUSC, while inhibition of HDAC6 significantly suppresses LUSC cell growth. And, GATA6 overexpression reverses HDAC6-mediated elevated growth and migration of LUSC cells. Compared to normal tissues, LUSC tissues exhibit elevated levels of HDAC6 expression, which were correlated with poor prognosis of LUSC patients.

Conclusion

Targeting HDAC6/GATA6 pathway may offer promising prospects for developing of novel therapeutic strategies against LUSC.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.