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KDM3A promotes oral squamous cell carcinoma cell proliferation and invasion via H3K9me2 demethylation-activated DCLK1

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Abstract

Background

Oral squamous cell carcinoma (OSCC) is a frequently-diagnosed malignancy with high potential for proliferation and invasion. Histone methylation is known as a crucial mechanism that regulates pathological processes in various cancers, including OSCC.

Objective

This study sought to delve into the molecular mechanism of lysine demethylase 3 A (KDM3A) in OSCC cell proliferation and invasion.

Methods

Expression levels of KDM3A, lysin-9 of di-methylated histone H3 (H3K9me2), and doublecortin-like kinase 1 (DCLK1) in cells were determined by reverse-transcription quantitative polymerase chain reaction or Western blot analysis. Cell proliferation and invasion were evaluated by cell counting kit-8, colony formation, and Transwell assays. The enrichment of KDM3A and H3K9me2 on the DCLK1 promoter was determined by chromatin immunoprecipitation assay. The functional rescue experiment was performed with DCLK1 overexpression vector and si-KDM3A in CAL-27 and SCC-9 cells.

Results

KDM3A was elevated in OSCC cells. KDM3A knockdown suppressed OSCC proliferation and invasion, along with increased H3K9me2 level in OSCC cells. KDM3A and H3K9me2 were enriched on the DCLK1 promoter and inhibiting H3K9me2 improved DCLK1 expression levels. DCLK1 overexpression neutralized the inhibition of KDM3A knockdown on OSCC proliferation and invasion.

Conclusions

KDM3A facilitated OSCC proliferation and invasion by eliminating H3K9me2 to upregulate DCLK1 expression levels.

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Data availability

All data generated or analyzed during this study are included in this article.

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Acknowledgements

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Author notes

  1. Lei Yang and Qiqiong Zhang are co-first authors and contributed equally to this work.

Authors and Affiliations

  1. Department of Prosthodontics, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing City, 163001, Heilongjiang Province, China

    Lei Yang, Qiqiong Zhang & Qiuye Yang

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  1. Lei Yang
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  2. Qiqiong Zhang
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Correspondence to Lei Yang.

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Yang, L., Zhang, Q. & Yang, Q. KDM3A promotes oral squamous cell carcinoma cell proliferation and invasion via H3K9me2 demethylation-activated DCLK1. Genes Genom 44, 1333–1342 (2022). https://doi.org/10.1007/s13258-022-01287-0

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