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The histone lysine demethylase 3 A (KDM3A) is vital for the regulation of cancer physiology and pathophysiology. The purpose of this study was to investigate the effect of KDM3A expression with triple-negative breast cancer (TNBC) invasion and metastasis. In our results, knockout of KDM3A in TNBC MDA-MB-231 cells promoted apoptosis and inhibited the proliferation, invasion and metastasis of MDA-MB-231 cells. In addition, we found that in vivo experiments indicated that the growth, invasion and metastasis of metastatic neoplasms were significantly inhibited by knockout of KDM3A in a TNBC metastasis model. These findings suggest that KDM3A may be a potential therapeutic target for the treatment and prevention of TNBC, providing a critical theoretical basis for the effective prevention or treatment of breast cancer disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The epigenetic modifier molecule lysine demethylase 3A (KDM3A) has been shown to help ameliorate cardiovascular diseases, but its effect on cardiac fibroblasts (CFs) remains unclear. Methods and results: We designed gain- and loss-of-function experiments to investigate the biological functions of KDM3A in CFs. Moreover, we used SIS3-HCl (a specific inhibitor of p-Smad3) to explore the underlying mechanism. Cell viability and migration were verified by CCK-8 and cell migration experiments, respectively, and the degree of fibrosis was measured by Western blot analysis. Our data revealed that KDM3A enhanced the proliferation and migration of CFs and increased the fibroblast-to-myofibroblast transition while enabling the Smad3 phosphorylation response to transforming growth factor beta1 (TGFβ1) stimulation. However, these effects were abolished by SIS3-HCl. Furthermore, KDM3A inhibition obviously protected against cardiac myofibroblast transdifferentiation under TGFβ1 stimulation. Conclusions: KDM3A may act as a novel regulator of cardiac myofibroblast transdifferentiation through its ability to modulate the phosphorylation of Smad3 following TGFβ1 stimulation. [ABSTRACT FROM AUTHOR]

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between KDM3A expression and the clinicopathological parameters of patients with epithelial ovarian cancer (EOC). KDM3A expression was analyzed using immunohistochemistry in EOC tissue microarray containing 90 paired cases of EOC and matched normal control. The expression level of KDM3A protein in EOC tissues was significantly higher than that of adjacent normal control tissues. In addition, positive expression of KDM3A correlated with the metastases. Furthermore, Kaplan-Meier survival analysis showed that a high expression level of KDM3A resulted in a significantly poor prognosis of EOC patients. Knock-down of KDM3A could suppress both the proliferation, migration and invasion in vitro EOC cell lines OV-2008 and ES-2. Additionally, knock-down of KDM3A not only could enhance cellular apoptosis induced by Cisplatin and Paclitaxel, but also induced some pro-apoptotic genes expression. Our data is the first to demonstrate that increased KDM3A expression in EOC is significantly associated with metastases and poor prognosis; and that KDM3A promotes the proliferation, migration and invasion of EOC cells. Knock-down of KDM3A may be an important complement to EOC that is resistant or refractory to chemotherapy. [ABSTRACT FROM AUTHOR]