Lysophosphatidic Acid Induces MDA-MB-231 Breast Cancer Cells Migration through Activation of PI3K/PAK1/ERK Signaling

Enhanced motility of cancer cells is a critical step in promoting tumor metastasis. Lysophosphatidic acid (LPA), representing the major mitogenic activity in serum, stimulates migration in various types of cancer cells. However, the underlying signaling mechanisms for LPA-induced motility of cancer cells remain to be elucidated.In this study, we found that LPA dose-dependently stimulated migration of MDA-MB-231 breast cancer cells, with 10 µM being the most effective. LPA also increased ERK activity and the MEK inhibitor U0126 could block LPA-induced ERK activity and cell migration. In addition, LPA induced PAK1 activation while ERK activation and cell migration were inhibited by ectopic expression of an inactive mutant form of PAK1 in MDA-MB-231 cells. Furthermore, LPA increased PI3K activity, and the PI3K inhibitor LY294002 inhibited both LPA-induced PAK1/ERK activation and cell migration. Moreover, in the breast cancer cell, LPA treatment resulted in remarkable production of reactive oxygen species (ROS), while LPA-induced ROS generation, PI3K/PAK1/ERK activation and cell migration could be inhibited by N-acetyl-L-Cysteine, a scavenger of ROS.Taken together, this study identifies a PI3K/PAK1/ERK signaling pathway for LPA-stimulated breast cancer cell migration. These data also suggest that ROS generation plays an essential role in the activation of LPA-stimulated PI3K/PAK1/ERK signaling and breast cancer cell migration. These findings may provide a basis for designing future therapeutic strategy for blocking breast cancer metastasis

Extracellular vesicles-mediated noncoding RNAs transfer in cancer

Abstract Extracellular vesicles (EVs) are small membranous vesicles secreted from numerous cell types and have been found involved in cell-to-cell communication by transferring noncoding RNAs (ncRNAs) including microRNAs, long noncoding RNAs, and circular RNAs. Emerging evidence shows that EV-associated ncRNAs play important roles in a wide range of diseases, particularly in cancer where they function through regulating protein expression of the pivotal genes that make contributions to tumorigenesis. Given their stability and abundance in serum, EV-associated ncRNAs can act as new diagnostic biomarkers and new therapeutic targets for cancer. Herein, we review the properties of EV-associated ncRNAs, their functions, and potential significance in cancer

The spatial-temporal characteristics and health impacts of ambient fine particulate matter in China

Airborne particulate matter presents a serious health threat to human beings, but in China there have until now been few epidemiological studies, especially regarding the impact of ambient fine particulate matter (PM2.5). This study explored first the temporal and spatial characteristics of ambient airborne PM2.5 in China, 2013. Mortality, respiratory diseases, cardiovascular diseases, and chronic bronchitis were then evaluated as four health endpoints attributed to PM2.5. The results showed that the average annual PM2.5 concentration was 72.71 μg/m3; the PM2.5 concentration was below 35 μg/m3 for only 6% of the time, for the whole year. In terms of the PM2.5 concentration, January (133.10 μg/m3) and December (120.19 μg/m3) were the most polluted months, whereas July (38.76 μg/m3) and August (41.31 μg/m3) were the least polluted months. The most highly polluted areas were concentrated in North China. In terms of the health endpoints attributable to PM2.5, there were 763,595 mortality, 149,754 cardiovascular diseases, 446,035 respiratory diseases, and 2,389,035 chronic bronchitis cases. Results were very important to clarify the current PM2.5 pollution situation and the health impact of PM2.5 in China. And also provided a reference for the assessing damage caused by PM2.5 pollution

Reprint of:The spatial-temporal characteristics and health impacts of ambient fine particulate matter in China

Airborne particulate matter presents a serious health threat to human beings, but in China there have until now been few epidemiological studies, especially regarding the impact of ambient fine particulate matter (PM2.5). This study explored first the temporal and spatial characteristics of ambient airborne PM2.5 in China, 2013. Mortality, respiratory diseases, cardiovascular diseases, and chronic bronchitis were then evaluated as four health endpoints attributed to PM2.5. The results showed that the average annual PM2.5 concentration was 72.71 μg/m3; the PM2.5 concentration was below 35 μg/m3 for only 6% of the time, for the whole year. In terms of the PM2.5 concentration, January (133.10 μg/m3) and December (120.19 μg/m3) were the most polluted months, whereas July (38.76 μg/m3) and August (41.31 μg/m3) were the least polluted months. The most highly polluted areas were concentrated in North China. In terms of the health endpoints attributable to PM2.5, there were 763,595 mortality, 149,754 cardiovascular diseases, 446,035 respiratory diseases, and 2,389,035 chronic bronchitis cases. Results were very important to clarify the current PM2.5 pollution situation and the health impact of PM2.5 in China. And also provided a reference for the assessing damage caused by PM2.5 pollution

Genome-wide analysis of basic/helix-loop-helix gene family in peanut and assessment of its roles in pod development

<div><p>The basic/helix-loop-helix (bHLH) proteins constitute a superfamily of transcription factors that are known to play a range of regulatory roles in eukaryotes. Over the past few decades, many bHLH family genes have been well-characterized in model plants, such as <i>Arabidopsis</i>, rice and tomato. However, the bHLH protein family in peanuts has not yet been systematically identified and characterized. Here, 132 and 129 bHLH proteins were identified from two wild ancestral diploid subgenomes of cultivated tetraploid peanuts, <i>Arachis duranensis</i> (AA) and <i>Arachis ipaensis</i> (BB), respectively. Phylogenetic analysis indicated that these <i>bHLH</i>s could be classified into 19 subfamilies. Distribution mapping results showed that peanut <i>bHLH</i> genes were randomly and unevenly distributed within the 10 AA chromosomes and 10 BB chromosomes. In addition, 120 <i>bHLH</i> gene pairs between the AA-subgenome and BB-subgenome were found to be orthologous and 101 of these pairs were highly syntenic in AA and BB chromosomes. Furthermore, we confirmed that 184 <i>bHLH</i> genes expressed in different tissues, 22 of which exhibited tissue-specific expression. Meanwhile, we identified 61 <i>bHLH</i> genes that may be potentially involved in peanut-specific subterranean. Our comprehensive genomic analysis provides a foundation for future functional dissection and understanding of the regulatory mechanisms of bHLH transcription factors in peanuts.</p></div

Genome-wide characterization, evolutionary analysis of WRKY genes in Cucurbitaceae species and assessment of its roles in resisting to powdery mildew disease.

The WRKY proteins constitute a large family of transcription factors that have been known to play a wide range of regulatory roles in multiple biological processes. Over the past few years, many reports have focused on analysis of evolution and biological function of WRKY genes at the whole genome level in different plant species. However, little information is known about WRKY genes in melon (Cucumis melo L.). In the present study, a total of 56 putative WRKY genes were identified in melon, which were randomly distributed on their respective chromosomes. A multiple sequence alignment and phylogenetic analysis using melon, cucumber and watermelon predicted WRKY domains indicated that melon WRKY proteins could be classified into three main groups (I-III). Our analysis indicated that no recent duplication events of WRKY genes were detected in melon, and strong purifying selection was observed among the 85 orthologous pairs of Cucurbitaceae species. Expression profiles of CmWRKY derived from RNA-seq data and quantitative RT-PCR (qRT-PCR) analyses showed distinct expression patterns in various tissues, and the expression of 16 CmWRKY were altered following powdery mildew infection in melon. Besides, we also found that a total of 24 WRKY genes were co-expressed with 11 VQ family genes in melon. Our comparative genomic analysis provides a foundation for future functional dissection and understanding the evolution of WRKY genes in cucurbitaceae species, and will promote powdery mildew resistance study in melon

Information on the consensus motif and conserved amino acid sequences in the bHLH domain.

<p>Information on the consensus motif and conserved amino acid sequences in the bHLH domain.</p

The chromosomal location and identification of orthologous genes between AA-subgenome and BB-subgenome.

<p>The chromosomal location and identification of orthologous genes between AA-subgenome and BB-subgenome.</p

The distribution of introns within domains of peanut bHLH proteins.

<p>All patterns are color coded and defined as I to X. Introns are indicated by triangles and numbered (1 to 3) based on those present in the bHLH region of Aradu.QV5DJ (shown at the top). The numbers of proteins with each pattern is given at the right.</p