Repression of Biotin-Related Proteins by Benzo[a]Pyrene-Induced Epigenetic Modifications in Human Bronchial Epithelial Cells.

Benzo[a]pyrene (B[a]P) exposure has been associated with the alteration in epigenetic marks that are involved in cancer development. Biotinidase (BTD) and holocarboxylase synthetase (HCS) are 2 major enzymes involved in maintaining the homeostasis of biotinylation, and the deregulation of this pathway has been associated with a number of cancers. However, the link between B[a]P exposure and the dysregulation of BTD/HCS in B[a]P-associated tumorigenesis is unknown. Here we showed that the expression of both BTD and HCS was significantly decreased upon B[a]P treatment in human bronchial epithelial (16HBE) cells. Benzo[a]pyrene exposure led to the global loss of DNA methylation by immunofluorescence, which coincided with the reduction in acetylation levels on histones H3 and H4 in 16HBE cells. Consistent with decreased histone acetylation, histone deacetylases (HDACs) HDAC2 and HDAC3 were significantly upregulated in a dosage-dependent manner. When DNA methylation or HDAC activity was inhibited, we found that the reduction in BTD and HCS was separately regulated through distinct epigenetic mechanisms. Together, our results suggested the potential link between B[a]P toxicity and deregulation of biotin homeostasis pathway in B[a]P-associated cancer development.

Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion.

Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

[The establishment of diagnosis model on occupational medicamentosa-like dermatitis induced by trichloroethylene].

OBJECTIVE: Based on magnetic beads based weak cation exchange chromatography (MB-WCX), matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and ClinProTools software, the polypeptides of serum about occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) patients were studied, and a diagnostic model of OMLDT was built. METHODS: According to diagnostic criteria of OMLDT, serum of 28 OMLDT patients and 28 controls which were diagnosed by Shenzhen prevention and treatment center for occupational disease were collected. With the combination of MB-WCX and MALDI-TOF-MS, the polypeptides fingerprint of serum of 14 OMLDT patients and 14 controls were detected, what's more, the ClinProTools software and SNN algorithm was used for screening characteristic polypeptides and establishing diagnostic model of OMLDT. Then other objects were applied to validate the model to evaluate accuracy. RESULTS: A total of 159 peaks were attained by ClinProTools software, of which 33 peaks were statistical content (P < 0.05). What is more, comparing with the control group, 20 peaks in case group were decreased, and 13 peaks were increased. Two peaks of them were identified, that is 2106.29 and 3263.78, to classify and determine that two groups by receiver operating characteristic curve (ROC) analysis.2D peaks distribution map certified this finding and the area under the ROC curve was closed to 1. A model was established by SNN algorithm, whose cross validation and recognition capability were 87.5% and 98.5%, respectively. Its sensitivity and specificity were 84.8% and 82.1%, separately, which displayed good separating capacity. CONCLUSION: In the combination of MB-WCX, MALDI-TOF-MS and ClinProTools software, specifical different polypeptides were screened and OMLDT diagnostic model was built primarily. Also, the model and the results were positively validated, which would play a significant role in early diagnosis.

Structure and Dielectric Behavior of Yb2O3-MgO Co-Doped 0.92BaTiO3-0.08(Na0.5Bi0.5)TiO3 Ferroelectric Relaxor.

Dielectric properties and structure of 0.015Yb2O3-xMgO doped 0.92BaTiO3-0.08(Na0.5Bi0.5)TiO3 ceramics with x = 0.0-0.025 have been investigated. As Yb2O3-MgO was added into the BT-NBT, the phase changes from tetragonal to pseudo-cubic, with the tetragonality c/a decreases from 1.011 to 1.008 and XRD peaks broadened. The combined study of XRD and TEM image revealed a formation of core-shell structure in grains with core of 400-600 nm and the shell of a thickness 60-200 nm. There is a slowly phase transition against temperature from the variable temperature Raman analysis. The ferroelectric relaxor peak of BT-NBT decreases from ~4000 to ~2000 and a new broad dielectric peak with an equivalent maximum (εr'~2300) appears in the temperature dependent dielectric constant curve (εr'-T), which produces a flat εr'-T curve. Sample 0.92BaTiO3-0.08(Na0.5Bi0.5)TiO3-0.015Yb2O3-0.005 MgO and 0.92BaTiO3-0.08(Na0.5Bi0.5)TiO3-0.015Yb2O3-0.01MgO give a εr' variation within ±14% and ±10% in 20-165 °C. The core-shell microstructure should take account for the flattened εr'-T behavior of these samples.

Effect of hexavalent chromium on histone biotinylation in human bronchial epithelial cells.

Chromium is a potent human mutagen and carcinogen. The capability of chromium to cause cancers has been known for more than a century, and numerous epidemiological studies have been performed to determine its carcinogenicity. In the post-genome era, cancer has been found to relate to epigenetic mutations. However, very few researches have focused on hexavalent chromium (Cr(VI))-induced epigenetic alterations. The present study was designed to investigate whether Cr(VI) would affect the level of a newfound epigenetic modification: histone biotinylation. Histone acetylation and histone biotinylation were studied in detail using human bronchial epithelial (16HBE) cells as an in vitro model after Cr(VI) treatment. Our study showed that Cr(VI) treatment decreased histone acetylation level in 16HBE cells. In addition, low doses of Cr(VI) (≤0.6µM) elevated the level of histone biotinylation. Furthermore, immunoblot analysis of biotinidase (BTD), a major protein which maintains homeostasis of histone biotinylation, showed that the distribution of BTD became less even and more concentrated at the nuclear periphery in cells exposed to Cr(VI). Moreover, Cr(VI)-induced histone deacetylation may take part in the regulation of histone biotinylation. Together, our study provides new insight into the mechanisms of Cr(VI)-induced epigenetic regulation that may contribute to the chemoprevention of Cr(VI)-induced cancers and may have important implications for epigenetic therapy.