The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas

<p>Abstract</p> <p>Background</p> <p>Claudin-6 is a candidate tumor suppressor gene in breast cancer, and has been shown to be regulated by DNA methylation and histone modification in breast cancer lines. However, the expression of claudin-6 in breast invasive ductal carcinomas and correlation with clinical behavior or expression of other markers is unclear. We considered that the expression pattern of claudin-6 might be related to the expression of DNA methylation associated proteins (methyl-CpG binding protein 2 (MeCP2) and DNA methyltransferase 1 (DNMT1)) and histone modification associated proteins (histone deacetylase 1 (HDAC1), acetyl-histone H3 (H3Ac) and acetyl- histone H4 (H4Ac)).</p> <p>Methods</p> <p>We have investigated the expression of claudin-6, MeCP2, HDAC1, H3Ac and H4Ac in 100 breast invasive ductal carcinoma tissues and 22 mammary gland fibroadenoma tissues using immunohistochemistry.</p> <p>Results</p> <p>Claudin-6 protein expression was reduced in breast invasive ductal carcinomas (<it>P </it>< 0.001). In contrast, expression of MeCP2 (<it>P </it>< 0.001), DNMT1 (<it>P </it>= 0.001), HDAC1 (<it>P </it>< 0.001) and H3Ac (<it>P </it>= 0.004) expressions was increased. Claudin-6 expression was inversely correlated with lymph node metastasis (<it>P </it>= 0.021). Increased expression of HDAC1 was correlated with histological grade (<it>P </it>< 0.001), age (<it>P </it>= 0.004), clinical stage (<it>P </it>= 0.007) and lymph node metastasis (<it>P </it>= 0.001). H3Ac expression was associated with tumor size (<it>P </it>= 0.044) and clinical stage of cancers (<it>P </it>= 0.034). MeCP2, DNMT1 and H4Ac expression levels did not correlate with any of the tested clinicopathological parameters (<it>P </it>> 0.05). We identified a positive correlation between MeCP2 protein expression and H3Ac and H4Ac protein expression.</p> <p>Conclusions</p> <p>Our results show that claudin-6 protein is significantly down-regulated in breast invasive ductal carcinomas and is an important correlate with lymphatic metastasis, but claudin-6 down-regulation was not correlated with upregulation of the methylation associated proteins (MeCP2, DNMT1) or histone modification associated proteins (HDAC1, H3Ac, H4Ac). Interestingly, the expression of MeCP2 was positively correlated with the expression of H3Ac and H3Ac protein expression was positively correlated with the expression of H4Ac in breast invasive ductal carcinoma</p> <p>Virtual slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/4549669866581452</url></p

New insights into the regulation of METTL3 and its role in tumors

Abstract As one of the most abundant epigenetic modifications in RNA, N6-methyladenosine (m6A) affects RNA transcription, splicing, stability, and posttranscriptional translation. Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, dynamically regulates target genes expression through m6A modification. METTL3 has been found to play a critical role in tumorigenesis, tumor growth, metastasis, metabolic reprogramming, immune cell infiltration, and tumor drug resistance. As a result, the development of targeted drugs against METTL3 is becoming increasingly popular. This review systematically summarizes the factors that regulate METTL3 expression and explores the specific mechanisms by which METTL3 affects multiple tumor biological behaviors. We aim to provide fundamental support for tumor diagnosis and treatment, at the same time, to offer new ideas for the development of tumor-targeting drugs. Video Abstrac

CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers

Claudins (CLDNs) are the most important tight junction proteins, which are mainly expressed in endothelial cells or epithelial cells in a tissue-specific manner. As a member of the CLDNs family, CLDN6 is highly expressed in fetal tissues such as the stomach, pancreas, lung, and kidney, but is not expressed in corresponding adult tissues. The expression of CLDN6 is regulated by a variety of factors, including but not limited to stimuli and transcription factors, DNA methylation, and post-translational modifications. CLDN6 has been found to have a key role in the formation of barriers, especially the lung epithelial barrier and the epidermal permeability barrier (EPB). Importantly, the roles of CLDN6 in cancers have gained focus and are being investigated in recent years. Strong evidence indicates that the altered expression of CLDN6 is linked to the development of various cancers. Malignant phenotypes of tumors affected by CLDN6 include proliferation and apoptosis, migration and invasion, and drug resistance, which are regulated by CLDN6-mediated key signaling pathways. Given the important role in tumors and its low or no expression in normal tissues, CLDN6 is an ideal target for tumor therapy. This review aims to provide an overview of the structure and regulation of CLDN6, and its traditional barrier function, with a special emphasis on its emerging roles in cancers, including its impact on the malignant phenotypes, signal-modulating effects, the prognosis of tumor patients, and clinical applications in cancers

Poly[hexaaqua(&#956;9-cyclohexane-1,2,3,4,5,6-hexacarboxylato)trimanganese(II)]

The asymmetric unit of the title compound, [Mn3(C12H6O12)(H2O)6]n, comprises one MnII ion, one third of a cyclohexane-1,2,3,4,5,6-hexacarboxylate anion and two aqua ligands. The anion is completed by application of a -3 axis. The MnII ion is six-coordinated by six O atoms from two aqua ligands and three different cyclohexacarboxylate anions in an octahedral geometry. The six carboxylate groups adopt a bridging bidentate mode to ligate the MnII ions. Thus, each cyclohexane-1,2,3,4,5,6-hexacarboxylate anion adopts a &#956;9-connected mode, ligating nine different MnII ions and forming a three-dimensional framework. In the framework, there are strong O&#8212;H...O hydrogen-bonding interactions, which further stabilize the crystal structure