MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1α/HIF-1β

<p>Abstract</p> <p>Background</p> <p>In prostate cancer (PCa), the common treatment involving androgen ablation alleviates the disease temporarily, but results in the recurrence of highly aggressive and androgen-independent metastatic cancer. Therefore, more effective therapeutic approaches are needed. It is known that aberrant epigenetics contributes to prostate malignancy. Unlike genetic changes, these epigenetic alterations are reversible, which makes them attractive targets in PCa therapy to impede cancer progression. As a histone methyltransferease, Ezh2 plays an essential role in epigenetic regulation. Since Ezh2 is overexpressed and acts as an oncogene in PCa, it has been proposed as a bona fide target of PCa therapy. MicroRNAs (miRNAs) regulate gene expression through modulating protein translation. Recently, the contribution of miRNAs in cancer development is increasingly appreciated. In this report, we present our study showing that microRNA-101 (miR-101) inhibits Ezh2 expression and differentially regulates prostate cancer cells. In addition, the expression of miR-101 alters upon androgen treatment and HIF-1α/HIF-1β induction.</p> <p>Result</p> <p>In our reporter assays, both miR-101 and miR-26a inhibit the expression of a reporter construct containing the 3'-UTR of Ezh2. When ectopically expressed in PC-3, DU145 and LNCaP cells, miR-101 inhibits endogenous Ezh2 expression in all three cell lines, while miR-26a only decreases Ezh2 in DU145. Ectopic miR-101 reduces the invasion ability of PC-3 cells, while restored Ezh2 expression rescues the invasiveness of PC-3 cells. Similarly, miR-101 also inhibits cell invasion and migration of DU145 and LNCaP cells, respectively. Interestingly, ectopic miR-101 exhibits differential effects on the proliferation of PC-3, DU-145 and LNCaP cells and also causes morphological changes of LNCaP cells. In addition, the expression of miR-101 is regulated by androgen receptor and HIF-1α/HIF-1β. While HIF-1α/HIF-1β induced by deferoxamine mesylate (DFO) decreases miR-101 levels, the overall effects of R-1881 on miR-101 expression are stimulatory.</p> <p>Conclusions</p> <p>This study indicates that miR-101 targets Ezh2 and decreases the invasiveness of PCa cells, suggesting that miR-101 introduction is a potential therapeutic strategy to combat PCa. MiR-101 differentially regulates prostate cell proliferation. Meanwhile, the expression of miR-101 is also modulated at different physiological conditions, such as androgen stimulation and HIF-1α/HIF-1β induction.</p

Enhancing Landslide Susceptibility Modelling Through a Novel Non-landslide Sampling Method and Ensemble Learning Technique

In recent years, several catastrophic landslide events have been observed throughout the globe, threatening to lives and infrastructures. To minimize the impact of landslides, the need of landslide susceptibility map is important. The study aims to extract high-quality non-landslide samples and improve the accuracy of landslide susceptibility modelling (LSM) outcomes by applying a coupled method of ensemble learning and Machine Learning (ML). The Zigui-Badong section of the Three Gorges Reservoir area (TGRA) in China was considered in the present study. Twelve influencing factors were selected as inputs for LSM, and the relationship between each causal factor and landslide spatial development was quantitatively analyzed. A total of 179 landslides have been used in the present study. About 70% of the landslide pixels were randomly considered for training, and the remaining 30% were used for validation. Logistic Regression (LR) model was applied to produce an initial susceptibility map, and the non-landslide samples were selected within the classified low-susceptibility zone. Subsequently, two ML classifiers – the Classification and Regression Tree (CART), and the Multi-Layer Perceptron (MLP), and four coupling models – the CART-Bagging, CART-Boosting, MLP-Bagging, and MLP-Boosting, were utilized for LSM. Finally, the receiver operating characteristics (ROC) curve and statistical analysis were applied for accuracy assessment. The results show that altitude and distance to rivers were the main causal factors of landslides in the study area. The LR-MLP-Boosting performed the best with an accuracy of 0.986 followed by the LR-CART-Bagging, LR-CART-Boosting, and LR-MLP-Bagging. Accuracy comparisons demonstrate that ensemble learning algorithm can notably enhance the LSM performance of ML classifiers, and the Boosting algorithm marginally outperforms the Bagging algorithm. Moreover, the LR model can effectively constrain the selection range of non-landslide samples. The non-landslide sampling method constrained by LR yields higher quality samples compared to raditional random sampling method with no constraints, which develops a more excellent LSM

Yin Yang 1 contains G-quadruplex structures in its promoter and 5′-UTR and its expression is modulated by G4 resolvase 1

Yin Yang 1 (YY1) is a multifunctional protein with regulatory potential in tumorigenesis. Ample studies demonstrated the activities of YY1 in regulating gene expression and mediating differential protein modifications. However, the mechanisms underlying YY1 gene expression are relatively understudied. G-quadruplexes (G4s) are four-stranded structures or motifs formed by guanine-rich DNA or RNA domains. The presence of G4 structures in a gene promoter or the 5′-UTR of its mRNA can markedly affect its expression. In this report, we provide strong evidence showing the presence of G4 structures in the promoter and the 5′-UTR of YY1. In reporter assays, mutations in these G4 structure forming sequences increased the expression of Gaussia luciferase (Gluc) downstream of either YY1 promoter or 5′-UTR. We also discovered that G4 Resolvase 1 (G4R1) enhanced the Gluc expression mediated by the YY1 promoter, but not the YY1 5′-UTR. Consistently, G4R1 binds the G4 motif of the YY1 promoter in vitro and ectopically expressed G4R1 increased endogenous YY1 levels. In addition, the analysis of a gene array data consisting of the breast cancer samples of 258 patients also indicates a significant, positive correlation between G4R1 and YY1 expressio

SOX7: From a developmental regulator to an emerging tumor suppressor

SOX7 belongs to the SOX (SRY-related HMG-box) family of transcription factors that have been shown to regulate multiple biological processes, such as hematopoiesis, vasculogenesis and cardiogenesis during embryonic development. Recent studies indicate that several SOX family members play important roles in tumorigenesis. In this review, we introduce SOX7 gene and protein structures, and discuss its expression and functional role in cancer development and progression. SOX7 is frequently downregulated in many human cancers and its reduced expression correlates with poor prognoses of several cancers. Functional studies reveal many tumor suppressive properties of SOX7 in prostate, colon, lung, and breast cancers. To date, although a few target genes of SOX7 have been identified, SOX7-mediated gene expression has not been investigated in a cancer-relevant context. Our recent studies not only for the first time demonstrate a tumor suppressive role of SOX7 in a xenograft mouse model, but also unravel that many genes regulating cell death, growth and apoptosis are affected by SOX7, strongly supporting a pivotal role of SOX7 in tumorigenesis. Thus, currently available data clearly indicate a tumor suppressive role of SOX7, but the mechanisms underlying its gene expression and tumor suppressive activity remain undetermined. The research of SOX7 in cancers remains a fertile area to be explored. Histol Histopathol 29, 439-445 (2014

Effects of Ecological Restoration on the Distribution of Soil Particles and Organic Carbon in Alpine Regions

This study discusses the impact of two different ecological restoration approaches on the distribution of soil particle size and organic carbon, expecting to provide references for research on the effects of ecological restoration on the soil carbon pool in alpine regions. By replacing the method of time sampling with spatial sampling, grasslands enclosed only in the growing season and woodlands enclosed all year round were respectively selected as the research objects. Through centrifugation, the soil samples were classified by grain size into sand (50&ndash;2000 &mu;m), silt (2&ndash;50 &mu;m), and clay (&lt;2 &mu;m) to analyze the distribution of organic carbon in soil particles of different sizes. The major findings were as follows. First, sand accounted for the largest proportion of all the soil components in the grasslands and woodlands that had been restored for different years, followed by silt and clay. Second, most of the organic carbon in the grasslands and woodlands was from sand and silt. As the restoration years increased, the proportion of organic carbon in clay grew in fluctuation. In short, both ecological restoration approaches have improved the soil structure and raised the content of soil organic carbon (SOC). Specifically, the restoration scheme of the woodlands exerted a more significant influence on the soil components and the distribution of organic carbon than that of the grasslands

Effects of Ecological Restoration on the Distribution of Soil Particles and Organic Carbon in Alpine Regions

This study discusses the impact of two different ecological restoration approaches on the distribution of soil particle size and organic carbon, expecting to provide references for research on the effects of ecological restoration on the soil carbon pool in alpine regions. By replacing the method of time sampling with spatial sampling, grasslands enclosed only in the growing season and woodlands enclosed all year round were respectively selected as the research objects. Through centrifugation, the soil samples were classified by grain size into sand (50–2000 μm), silt (2–50 μm), and clay (<2 μm) to analyze the distribution of organic carbon in soil particles of different sizes. The major findings were as follows. First, sand accounted for the largest proportion of all the soil components in the grasslands and woodlands that had been restored for different years, followed by silt and clay. Second, most of the organic carbon in the grasslands and woodlands was from sand and silt. As the restoration years increased, the proportion of organic carbon in clay grew in fluctuation. In short, both ecological restoration approaches have improved the soil structure and raised the content of soil organic carbon (SOC). Specifically, the restoration scheme of the woodlands exerted a more significant influence on the soil components and the distribution of organic carbon than that of the grasslands

The Partitioning of Catchment Evapotranspiration Fluxes as Revealed by Stable Isotope Signals in the Alpine Inland River Basin

Evapotranspiration is an important process in the water budget of an ecosystem. Quantifying the components of evapotranspiration is of great significance in revealing the ecohydrological process of alpine inland river basins. In this study, the evapotranspiration fluxes in the Shaliu River basin were classified by hydrogen and oxygen stable isotope technology and remote sensing technology. The results showed the following: (1) The average value of soil fractional evaporation (E1) in the summer of 2018 and 2019 was 7.59 mm and 2.10 mm, respectively. (2) The average ratio of soil evaporation (Esoil) in the summer of 2018 was 48.82%, 68.11%, 54.99%, respectively. The average ratio of Esoil in the summer of 2019 was 66.86%, 57.50%, 55.53%, respectively. The average value of Esoil in the summer of 2018 and 2019 was 42.84 mm and 35.36 mm, respectively. (3) The average ratio of vegetation transpiration (T) in the summer of 2018 was 51.18%, 31.89%, and 45.01%, respectively. The average ratio of T in the summer of 2019 was 33.14%, 42.50%, and 44.47%, respectively. The average value of T in the summer of 2018 and 2019 was 32.59 mm and 26.23 mm, respectively. Obviously, the soil fractionation was stronger in the summer of 2018 than that in the summer of 2019. At the same time, both soil evaporation and plant transpiration in summer 2018 were higher than those in summer 2019, and soil evaporation in the Shaliu River basin was greater than plant transpiration in summer during the study period. The results of this study can provide data reference for mastering the eco-hydrological process of the Shaliu River basin

Characteristics and Potential Ecological Risks of Heavy Metal Content in the Soil of a Plateau Alpine Mining Area in the Qilian Mountains

In recent years, the ecological and environmental problems caused by mining in the Qilian Mountains have attracted considerable attention, and the government has carried out a number of comprehensive ecological environment remediation projects there, among which ecological restoration in the Qilian Mountain alpine mining area is an essential task. As a result, heavy metals have been studied in the soil of the Qilian Mountain alpine mining area. This can provide a scientific basis and data support for the establishment of a demonstration index for monitoring ecological environmental restoration in mining areas. In order to understand the content and contamination status of heavy metals in the soil surrounding the alpine mining area of Qilian Mountain, 56 soil samples were collected to determine the levels of eight heavy metals, including Cd, Hg, As, Pb, Cr, Cu, Zn, and Ni. The spatial distribution of heavy metals in the soil of the study area was analyzed based on a statistical approach. The single-factor pollution index (Pi), Nemerow comprehensive pollution index (PN), geoaccumulation index (Igeo), and potential ecological risk index (RI) were used to evaluate soil heavy metal pollution and potential ecological risk. Principal component analysis (PCA), positive matrix factorization (PMF) models, and geostatistical analysis were also used to investigate the source of heavy metals. The results show that the average Cd, As, Cr, Cu, Zn, and Ni content of the grassland soil around the mining area exceeds the soil background values in both Qinghai Lake Basin and Qinghai Province. The spatial distribution of the eight heavy metal elements in soil showed an island-like pattern, with high-value areas of each metal element appearing, indicating that human activities in the study area had negative effects on the soil environment. The value of the single pollution index showed that levels of Ni, Cd, Cu, Cr, Hg, and As pollution were low, while there was no Pb or Zn pollution. The Nemerow integrated pollution index had an average value of 1.39, indicating a slight pollution trend. The average values of Cr and Zn in the geoaccumulation index ranged from 0 to 1, indicating mild to moderate contamination in the studied region. The average value of the integrated ecological risk index in the study area was 135.43, which is in the intermediate ecological risk range. In descending order of size, the average ecological risk index of each heavy metal element was Hg > Cd> As > Ni > Cu > Pb > Cr > Zn. From the perspective of the spatial distribution pattern of ecological risk, the two high-value discriminants were in the western part of the study area, close to the mining area. Zn, Cu, Pb, and Cd in soils were mainly affected by human activity, while Cr and Ni were mainly affected by soil geochemistry. Cd is the main contaminant in the study area, and soil Cd contamination of the grassland in the study area must be considered