Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers.

Background: Impairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus higher levels of benzene exposure. This observation is potentially explained by saturation of enzymatic systems.

Correction: Zhu et al. A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-like Properties and Invasion in Human Bladder Cancer. 2019, , 349.

In the original article [...

DNA Methyltransferase 1 Is Dysregulated in Parkinson's Disease via Mediation of miR-17.

Aberrant DNA methylation is closely associated with the pathogenesis of Parkinson's disease (PD). DNA methyltransferases (DNMTs) are the enzymes for establishment and maintenance of DNA methylation patterns. It has not been clearly defined how DNMTs respond in PD and what mechanisms are associated.

Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility. However, the etiology of NOA is largely unknown, resulting in a lack of clinical treatments. Here, we performed a comparative genome-wide profiling of DNA methylation and identified SOX30 as the most notably hyper-methylated gene at promoter in testicular tissues from NOA patients.

XIAP Interaction with E2F1 and Sp1 via its BIR2 and BIR3 domains specific activated MMP2 to promote bladder cancer invasion.

XIAP has generally been thought to function in bladder cancer. However, the potential function of structure-based function of XIAP in human BC invasion has not been well explored before. We show here that ectopic expression of the BIR domains of XIAP specifically resulted in MMP2 activation and cell invasion in XIAP-deleted BC cells, while Src was further defined as an XIAP downstream negative regulator for MMP2 activation and BC cell invasion.

Complementary biobank of rodent tissue samples to study the effect of World Trade Center exposure on cancer development.

World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological responses. These experiments aid in the interpretation of epidemiological observations and are useful for understanding the carcinogenesis process in the exposed human WTC cohort.

Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer.

Our previous studies have demonstrated that XIAP promotes bladder cancer metastasis through upregulating RhoGDIβ/MMP-2 pathway. However, the molecular mechanisms leading to the XIAP upregulation was unclear. In current studies, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BCs, and in mouse invasive BCs.

Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade.

An excess incidence of prostate cancer has been identified among World Trade Center (WTC) responders. In this study, we hypothesized that WTC dust, which contained carcinogens and tumor-promoting agents, could facilitate prostate cancer development by inducing DNA damage, promoting cell proliferation, and causing chronic inflammation. We compared expression of immunologic and inflammatory genes using a NanoString assay on archived prostate tumors from WTC Health Program (WTCHP) patients and non-WTC patients with prostate cancer.

Transcriptionally elevation of miR-494 by new ChlA-F compound via a HuR/JunB axis inhibits human bladder cancer cell invasion.

Muscle invasive bladder cancer (MIBC) is characterized by a poor overall survival rate in patients. Therefore, innovation and evaluation of idea anti-cancer compounds is of importance for reducing the mortality of MIBCs. The chemotherapeutic activity of ChlA-F, a novel C8 fluoride derivative of cheliensisin A with potent anti-neoplastic properties, was barely investigated.

A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-Like Properties and Invasion in Human Bladder Cancer.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 blockade have been identified to target immune checkpoints to treat human cancers with durable clinical benefit. Several studies reveal that the response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells. However, the mechanistic pathways that regulate PD-L1 protein expression are not understood.

The RING domain in the anti-apoptotic protein XIAP stabilizes c-Myc protein and preserves anchorage-independent growth of bladder cancer cells.

X-linked inhibitor of apoptosis protein (XIAP) suppresses apoptosis and plays key roles in the development, growth, migration, and invasion of cancer cells. Therefore, XIAP has recently attracted much attention as a potential antineoplastic therapeutic target, requiring elucidation of the molecular mechanisms underlying its biological activities. Here, using shRNA-mediated gene silencing, immunoblotting, quantitative RT-PCR, anchorage-independent growth assay, and invasive assay, we found that XIAP's RING domain, but not its BIR domain, is crucial for XIAP-mediated up-regulation of c-Myc protein expression in human bladder cancer (BC) cells.

CD44s is a crucial ATG7 downstream regulator for stem-like property, invasion, and lung metastasis of human bladder cancer (BC) cells.

Over half a million US residents are suffering with bladder cancer (BC), which costs a total $4 billion in treatment annually. Although recent studies report that autophagy-related gene 7 (ATG7) is overexpressed in BCs, the regulatory effects of ATG7 on cancer stem-like phenotypes and invasion have not been explored yet. Current studies demonstrated that the deficiency of ATG7 by its shRNA dramatically reduced sphere formation and invasion in vitro, as well as lung metastasis in vivo in human invasive BC cells.

NFκB2 p52 stabilizes rhogdiβ mRNA by inhibiting AUF1 protein degradation via a miR-145/Sp1/USP8-dependent axis.

Although overexpression of the non-canonical NFκB subunit p52 has been observed in several tumors, the function and mechanism of p52 in bladder cancer (BC) are less well understood. Here, we aimed at understanding the role and mechanism underlying p52 regulation of BC invasion. Human p52 was stably knockdown with shRNA targeting p52 in two bladder cancer cell lines (T24 and UMUC3).

ISO, via Upregulating MiR-137 Transcription, Inhibits GSK3β-HSP70-MMP-2 Axis, Resulting in Attenuating Urothelial Cancer Invasion.

Our most recent studies demonstrate that miR-137 is downregulated in human bladder cancer (BC) tissues, while treatment of human BC cells with isorhapontigenin (ISO) elevates miR-137 abundance. Since ISO showed a strong inhibition of invasive BC formation in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced invasive BC mouse model, the elucidation of a potential biological effect of miR-137 on antagonizing BC invasion and molecular mechanisms underlying ISO upregulation of miR-137 are very important. Here we discovered that ectopic expression of miR-137 led to specific inhibition of BC invasion in human high-grade BC T24T and UMUC3 cells, while miR-137 deletion promoted the invasion of both cells, indicating the inhibitory effect of miR-137 on human BC invasion.

New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating Sestrin-2 in human bladder cancer.

ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone isolates that show potent anti-tumor potential in vivo and vitro. However, the anti-cancer activity and its potential mechanisms underlying ChlA-F action have never been explored. In the present study, we evaluated the potency of ChlA-F on autophagy-mediated anchorage-independent growth inhibition in human high-grade invasive bladder cancer (BC) cells.

Decreased c-Myc mRNA Stability via the MicroRNA 141-3p/AUF1 Axis Is Crucial for p63α Inhibition of Cyclin D1 Gene Transcription and Bladder Cancer Cell Tumorigenicity.

Bladder cancer (BC) ranks as the sixth most common cancer in the United States and is the leading cause of death in patients with urinary malignancies. p63 is a member of the p53 family and is believed to function as a tumor suppressor in human BCs. Our most recent studies revealed a previously unknown function of the RING of XIAP in promoting microRNA 4295 (miR-4295) transcription, thereby reducing p63α protein translation and enhancing normal urothelial transformation, whereas p63α upregulates hsp70 transcription, subsequently activating the HSP70/Wasf3/Wave3/matrix metalloproteinase 9 (MMP-9) axis and promoting BC cell invasion via initiating the transcription factor E2F1.

PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein.

Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility. Our previous studies have identified that PHLPP2 participates in inhibition of transformation of human bronchial epithelial cells following lung carcinogen B[a]P/B[a]PDE exposure. However, nothing was known about the association of p27 with regulation of PHLPP2 expression and the role of PHLPP2 in bladder cancer (BC) invasion.

MicroRNA-411 Downregulation Enhances Tumor Growth by Upregulating MLLT11 Expression in Human Bladder Cancer.

Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in bladder cancer growth are not explored yet at present. Here, we screened 1,900 known miRNAs and first discovered that miR-411 was one of the major miRNAs, which was down-regulated in n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCs. This miR-411 down-regulation was also observed in human BC tissues and cell lines.

SOX30 Inhibits Tumor Metastasis through Attenuating Wnt-Signaling via Transcriptional and Posttranslational Regulation of β-Catenin in Lung Cancer.

Although high mortality of lung cancer is greatly due to distant metastasis, the mechanism of this metastasis remains unclear. Here, we investigate in lung cancer that SOX30 is sharply under-expressed in metastatic tumors compared with non-metastatic tumors, and suppresses plenty of metastasis related processes or pathways. SOX30 strongly inhibits tumor cell metastasis in vitro and in vivo.

Maximizing the Public Health Benefits from Climate Action.

Environmental benefits that could be gained by successful climate change mitigation actions are usually subject to long action-reaction time lags. Furthermore, the links of mitigation efforts to major sources of climate forcing greenhouse gas (GHG) emissions are often complex. Therefore, there is a risk that potentially effective mitigation strategies are discounted by policy-makers and the general public, and not given sufficient weight in economic models.

XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin-mediated Rho-GDIβ mRNA stability.

Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here, we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues.

Mitochondrial catalase induces cells transformation through nucleolin-dependent Cox-2 mRNA stabilization.

It's well documented that over-production of reactive oxygen species (ROS) causes detrimental damages to cells. While a low level of ROS, such as HO, functions as signaling transducer and motivates cell proliferation in both cancer and non-transformed stem cells. As a double-edged sword, the direct evidence for demonstrating the function of HO in the cause of tumor is barely characterized in intact cells.

RhoGDIβ promotes Sp1/MMP-2 expression and bladder cancer invasion through perturbing miR-200c-targeted JNK2 protein translation.

Our most recent studies demonstrate that RhoGDIβ is able to promote human bladder cancer (BC) invasion and metastasis in an X-link inhibitor of apoptosis protein-dependent fashion accompanied by increased levels of matrix metalloproteinase (MMP)-2 protein expression. We also found that RhoGDIβ and MMP-2 protein expressions are consistently upregulated in both invasive BC tissues and cell lines. In the present study, we show that knockdown of RhoGDIβ inhibited MMP-2 protein expression accompanied by a reduction of invasion in human BC cells, whereas ectopic expression of RhoGDIβ upregulated MMP-2 protein expression and promoted invasion as well.

p63α protein up-regulates heat shock protein 70 expression via E2F1 transcription factor 1, promoting Wasf3/Wave3/MMP9 signaling and bladder cancer invasion.

Bladder cancer (BC) is the sixth most common cancer in the United States and is the number one cause of death among patients with urinary system malignancies. This makes the identification of invasive regulator(s)/effector(s) as the potential therapeutic targets for managing BC a high priority. p63 is a member of the p53 family of tumor suppressor genes/proteins, plays a role in the differentiation of epithelial tissues, and is believed to function as a tumor suppressor.