Effects of RNA interference-mediated gene silencing of JMJD2A on human breast cancer cell line MDA-MB-231 in vitro

Abstract

Previous data demonstrate that JMJD2A is a cancer-associated gene and may be involved in human breast cancer by demethylation of H3K9me3. The aim of this study was to investigate depressive effects on JMJD2A by transfection with JMJD2A-sepcific siRNA in human breast cancer cell line MDA-MB-231 and effects on cell proliferation, invasion and migration. JMJD2A-specific siRNA was chemically synthesised and transfected into human breast cancer cell line MDA-MB-231. Expression levels of JMJD2A were detected by quantitative real-time PCR and Western blot analysis. Cells proliferation was evaluated by using flow cytometric anlysis and MTT assay. The abilities of invasion and migration were evaluated by cell migration and invasion assay with Boyden chambers. The results showed that the transfection was successful and expression levels of JMJD2A mRNA and protein in siRNA group were both down-regulated. By MTT assay, the mean actual absorbance in siRNA group was significantly lower than that in blank control group (P < 0.05) and negative control group (P < 0.05). In addition, the percentage of cells in G0/G1 phase in siRNA group was significantly more than that in blank control group (P < 0.05) and negative control group (P < 0.05). Furthermore, by cell invasion and migration assay, the decreased number of migrated cells in siRNA group was observed (P < 0.05). These data imply that silencing JMJD2A gene could result in cell cycle change and proliferation inhibition, and lead to suppress tumor cell invasion and migration. It provides a new perspective in understanding the pleiotropic functions of JMJD2A and its contribution to human breast cancer.

KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis

“…KDM4A is overexpressed in many cancer types including prostate, breast, lung and colon cancers and its expression is critical for cell proliferation (Berry et al, 2012; Chu et al, 2014; Cloos et al, 2006; Kim et al, 2012; Li et al, 2012; Li et al, 2011; Mallette and Richard, 2012). We previously reported that by selectively inhibiting KDM4A/4B with a small molecule inhibitor, the LNCaP prostate cancer cells displayed drastic growth retardation and increased apoptosis (Chu et al, 2014).…”

Expression and Effects of JMJD2A Histone Demethylase in Endometrial Carcinoma

“…Previous studies have demonstrated that JMJD2A is widely overexpressed in human tissue and cell lines, including breast cancer (Li et al, 2011;Berry et al, 2012), colon cancer (Kim et al, 2012), bladder cancer (Kauffman et al, 2011), and prostate cancer (Shin et al, 2007), although there is rarely evidence about expression of JMJD2A in endometrial carcinoma. We determined JMJD2A expression level in 56 endometrial carcinoma tissues and 20 normal endometrial tissues by immunohistochemistry.…”

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

“…For example, KDM4A interacts with class I HDACs and retinoblastoma protein (pRb), leading to HDAC-mediated gene inactivation (Gray et al, 2005). Therefore, the KDM4 demethylases are able to function as both transcriptional activators and repressors depending on which complexes they are associated with, and are involved in diverse cellular processes, such as regulation of cell cycle, DNA damage repair and even carcinogenesis (Cloos et al, 2006;Shin & Janknecht, 2007;Li et al, 2011;Berry et al, 2012;Kim et al, 2012;Mallette et al, 2012). An abundance of evidence has demonstrated that overexpression of KDM4 demethylases is involved in numerous cancers.…”