LncRNA-MALAT1 as a novel biomarker of cadmium toxicity regulates cell proliferation and apoptosis.

Cadmium (Cd) and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not well understood. This study aimed to investigate whether lncRNA-MALAT1 could serve as a novel biomarker of Cd toxicity in cells, animals and Cd-exposed workers, and regulate cell proliferation, apoptosis, migration and invasion. MALAT1 expression increased gradually in CdCl2 transformed 16HBE cells. The cell apoptosis, migration and invasion were significantly inhibited, and the mRNA and protein expression of FOXC2, STAT, BAX, EGFR, and TGF-ß1 reduced, but BCL-2 increased (P < 0.05) after silencing MALAT1 by siRNA in CdCl2 treated 16HBE cells of 15th and 35th passages. Cadmium increased MALAT1 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood MALAT1 expression and urinary/blood Cd concentrations, and there were significant correlations of MALAT1 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. This study suggests that the expression of MALAT1 is upregulated and regulates the cell cycle progression, proliferation, apoptosis, migration and invasion in Cd toxicity. MALAT1 may serve as a novel valuable biomarker of cadmium exposure and cadmium toxicity.

eIF3 regulates migration, invasion and apoptosis in cadmium transformed 16HBE cells and is a novel biomarker of cadmium exposure in a rat model and in workers.

Translation (eukaryotic) initiation factor 3 (eIF3 or TIF3) has been found to be a proto-oncogene in cadmium (Cd) response both in vitro and vivo, but whether eIF3 may serve as a biomarker of Cd exposure is still unclear. This study aimed to investigate whether eIF3 could serve as a novel biomarker of Cd toxicity in cells, animals and workers, and regulate the apoptosis, migration and invasion in human bronchial epithelial cell (16HBE cells) transformation with cadmium chloride (CdCl2). In CdCl2 transformed 16HBE cells, eIF3 expression increased gradually, and sequencing did not identify mutation and methylation of eIF3. In 16HBE cells with eIF3 silencing by siRNA and CdCl2 treated 16HBE cells of the 15th and 35th generations, the apoptosis, migration and invasion were significantly inhibited, and the expressions of relevant genes were also altered (P < 0.05). In CdCl2 treated rats, eIF3 mRNA expression increased to different extents in the blood, liver, kidney, heart and lung, and this increase was dependent on the Cd concentration (P < 0.05). The eIF3 mRNA expression was related to the mRNA expressions of AKT, BAX, BCL-2, E-CADHERIN, CASPASE-3, EGFR, FOXC2, STAT3, TGF-ß1 and VIMENTIN (P < 0.05). In 181 workers with Cd exposure, the eIF3 mRNA expression was positively related to the blood Cd, urine Cd and ß2-microglobulin content (P < 0.05). This study showed that abnormally expressed eIF3 may regulate the apoptosis, migration and invasion of 16HBE cells with Cd toxicity. This suggests that eIF3 may become a novel and valuable biomarker of Cd toxicity and Cd-induced effects, and may regulate apoptosis, migration and invasion of 16HBE cells. Thus, the detection of eIF3 expression is important for the monitoring of Cd toxicity in humans.

Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in a variety of physiological and pathophysiological processes. Our study was to investigate whether lncRNAs as novel expression signatures are able to modulate DNA damage and repair in cadmium(Cd) toxicity. There were aberrant expression profiles of lncRNAs in 35th Cd-induced cells as compared to untreated 16HBE cells. siRNA-mediated knockdown of ENST00000414355 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA-damage related genes (ATM, ATR and ATRIP), while increased the expressions of DNA-repair related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, RAD50, XRCC1 and BARD1). Cadmium increased ENST00000414355 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000414355 expression and urinary/blood Cd concentrations, and there were significant correlations of lncRNA-ENST00000414355 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. These results indicate that some lncRNAs are aberrantly expressed in Cd-treated 16HBE cells. lncRNA-ENST00000414355 may serve as a signature for DNA damage and repair related to the epigenetic mechanisms underlying the cadmium toxicity and become a novel biomarker of cadmium toxicity.

[Intracranial atherosclerotic middle cerebral arterial stenosis research based on 3.0 Tesla high-resolution magnetic resonance imaging: recent progress].

Intracranial atherosclerotic disease (ICAD) of a major intracranial artery, including middle cerebral artery (MCA),basilar artery, is the most common causes of stroke and is associated with a high risk of recurrent stroke in China. The difficulty to treatment these high-risk disease is to identify high-risk stroke subgroups and to develop more effective treatments (aggressive medical therapy/endovascular therapy). With the benefits, including non-invasive, in vivo, and no-ionizing radiation, 3.0 Tesla high-resolution magnetic resonance imaging (HR MRI) could be used to stratify high-risk patients, monitor progression of disease, and evaluate clinical efficacy, based on MCA wall structure and plaque characteristic. HR MRI has the latency of predicting high-risk patients benefit from endovascular therapy, having a broad application prospect during psot-SAMMPRIS era. The current research on MCA stenosis using HR MRI focuses on methodoiogy, diagnosis and differential diagnosis, etiology, and lacks of clinical efficiency evaluation and prognostic analysis of ICAD treatment, especially lacks the research on in-stent restenosis, which needs further investigation.

Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells.

Cadmium and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not entirely understood. Our study was designed to elucidate the mechanisms of DNA damage in cadmium-induced malignant transformation of human bronchial epithelial cells. We analyzed cell cycle, apoptosis, DNA damage, gene expression, genomic instability, and the sequence of exons in DNA repair genes in several kinds of cells. These cells consisted of untreated control cells, cells in the fifth, 15th, and 35th passage of cadmium-treated cells, and tumorigenic cells from nude mice using flow cytometry, Hoechst 33258 staining, comet assay, quantitative real-time polymerase chain reaction (PCR), Western blot analysis, random amplified polymorphic DNA (RAPD)-PCR, and sequence analysis. We observed a progressive increase in cell population of the G0/G1 phase of the cell cycle and the rate of apoptosis, DNA damage, and cadmium-induced apoptotic morphological changes in cerebral cortical neurons during malignant transformation. Gene expression analysis revealed increased expression of cell proliferation (PCNA), cell cycle (CyclinD1), pro-apoptotic activity (Bax), and DNA damage of the checkpoint genes ATM, ATR, Chk1, Chk2, Cdc25A. Decreased expression of the anti-apoptotic gene Bcl-2 and the DNA repair genes hMSH2, hMLH1, ERCC1, ERCC2, and hOGG1 was observed. RAPD-PCR revealed genomic instability in cadmium-exposed cells, and sequence analysis showed mutation of exons in hMSH2, ERCC1, XRCC1, and hOGG1 in tumorigenic cells. This study suggests that Cadmium can increase cell apoptosis and DNA damage, decrease DNA repair capacity, and cause mutations, and genomic instability leading to malignant transformation. This process could be a viable mechanism for cadmium-induced cancers.