PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression

Enhancer of zeste homolog 2 (EZH2) is a key epigenetic regulator that catalyzes the trimethylation of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associated factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 (PRC2). Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients predicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acetylation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.     

种植密度对北疆复播大豆光合特性及产量的影响

以大豆品种‘黑河43’为材料,于2012和2013年连续2年进行5种不同种植密度——37.5(A)、45.0(B)、52.5(C)、60.0(D)和67.5万株·hm-2(E)的田间复播试验,研究滴灌条件下密度对大豆功能叶叶绿素值(SPAD)、叶面积指数(LAI)、比叶面积(SLA)、大豆光合特性及产量构成因素的影响。结果显示:(1)密度对复播大豆苗期叶片SPAD值影响较小,苗期之后处理间差异显著,且整个生育期SPAD值均随着密度的增加而增大。(2)LAI在2年试验中均随着密度的增加而增大,均在鼓粒期左右达到峰值,处理E在2012年和2013年的最大值分别为6.24和5.56,较同期最低的处理A分别显著提高18.41%和36.17%;SLA随着密度的增加而增大,且在生长发育前期和后期处理间差异明显,中期差异相对较小。(3)叶片的净光合速率(Pn)、蒸腾速率(Tr)及气孔导度(Gs)均随着密度的增加而先增后降,且均以C处理最高,Pn、Gs在结荚期达到极值,而Tr在开花期最大;胞间CO2浓度(Ci)随着密度的增加呈现出先降后增的趋势,2012年和2013年均以C处理最低,分别为185.70和179.61μmol·mol-1。(4)各处理2年的籽粒产量均以中等密度的C处理达最高,2012年和2013年分别为3 205.0和3 142.53kg·hm-2,并分别比同年的其余处理显著高出1.42%~14.26%和1.08%~27.65%。研究表明,适宜密度的复播大豆不仅有较高的叶绿素含量,有利于群体对光能的利用,同时具有适宜的叶面积指数而不致植株郁闭,有效保证了群体内部与外界的气体交换,提高了光合速率和籽粒产量。     

基于信号放大技术的适体生物传感器研究进展

信号放大技术因其能实现低浓度分子检测,灵敏度高而在多个研究领域发展非常迅速。而适体作为识别分子已成功应用于多种生物传感器平台,在医疗诊断、环境检测、生化分析中显示出良好的应用前景。近年来,以适体为识别元件的生物传感器越来越受到人们的关注。综述了近3年来基于信号放大技术的适体生物传感器研究新发展。     

Excessive Retinoic Acid Impaired Proliferation and Differentiation of Human Fetal Palatal Chondrocytes (hFPCs)

Chondrocyte proliferation and differentiation is a fundamental process during hard palatogenesis. Excessive retinoic acid (RA), the biologically most active metabolite of vitamin A, has been reported to adversely affect chondrogenesis. The aim of this study was to investigate the mechanisms underlying RA‐induced chondrocyte differentiation by using human fetal palatal chondrocytes (hFPCs) aging about 9 weeks of amenorrhea. RA treatment inhibited proliferation and induced apoptosis in hFPCs. Alkaline phosphatase activity assay, quantitative alcian blue staining, and real‐time PCR analysis revealed that RA treatment stimulated hFPCs to undergo maturation and terminal differentiation, as demonstrated by decreased chondrogenic markers and increased osteogenic markers. Further studies demonstrated that RA treatment increased Wnt/β‐catenin signaling, as demonstrated by Wnt/β‐catenin target gene expression analysis and a luciferase‐based β‐catenin–activated reporter assay. To address the role of Wnt/β‐catenin signaling, we treated hFPCs with Dickkopf‐related protein 1, an extracellular inhibitor of Wnt/β‐catenin signaling, and the observed all‐trans retinoic acid–mediated increases in nuclear accumulation of β‐catenin, alkaline phosphatase activity, and type I collagen mRNA were attenuated, suggesting that RA modulated Wnt signaling at ligand–receptor level. In summary, excessive all‐trans retinoic acid inhibited proliferation and promoted ossification of hFPCs by upregulation of Wnt/β‐catenin signaling     

Research Article: Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination

Autophagy contributes to the pathogenesis of cancer, whereas toll-like receptors (TLRs) also play an important role in cancer development and immune escape. However, little is known about the potential interaction between TLR signaling and autophagy in cancer cells. Here we show that autophagy induced by TLR4 or TLR3 activation enhances various cytokine productions through promoting TRAF6 (TNF receptor-associated factor 6, E3 ubiquitin protein ligase) ubiquitination and thus facilitates migration and invasion of lung cancer cells. Stimulation of TLR4 and TLR3 with lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [poly(I:C)] respectively triggered autophagy in lung cancer cells. This was mediated by the adaptor protein, toll-like receptor adaptor molecule 1 (TICAM1/TRIF), and was required for TLR4- and TLR3-induced increases in the production of IL6, CCL2/MCP-1 [chemokine (C-C motif) ligand 2], CCL20/MIP-3α [chemokine (C-C motif) ligand 20], VEGFA (vascular endothelial growth factor A), and MMP2 [matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase)]. These cytokines appeared to be necessary for enhanced migration and invasion of lung cancer cells upon TLR activation. Remarkably, inhibition of autophagy by chemical or genetic approaches blocked TLR4- or TLR3-induced Lys63 (K63)-linked ubiquitination of TRAF6 that was essential for activation of MAPK and NFKB (nuclear factor of kappa light polypeptide gene enhancer in B-cells) pathways, both of which were involved in the increased production of the cytokines. Collectively, these results identify induction of autophagy by TLR4 and TLR3 as an important mechanism that drives lung cancer progression, and indicate that inhibition of autophagy may be a useful strategy in the treatment of lung cancer.     

Effect of Optimal Daily Fertigation on Migration of Water and Salt in Soil,Root Growth and Fruit Yield of Cucumber (Cucumis sativus L.) in Solar-Greenhouse

Inappropriate and excessive irrigation and fertilization have led to the predominant decline of crop yields, and water and fertilizer use efficiency in intensive vegetable production systems in China. For many vegetables, fertigation can be applied daily according to the actual water and nutrient requirement of crops. A greenhouse study was therefore conducted to investigate the effect of daily fertigation on migration of water and salt in soil, and root growth and fruit yield of cucumber. The treatments included conventional interval fertigation, optimal interval fertigation and optimal daily fertigation. Generally, although soil under the treatment optimal interval fertigation received much lower fertilizers than soil under conventional interval fertigation, the treatment optimal interval fertigation did not statistically decrease the economic yield and fruit nutrition quality of cucumber when compare to conventional interval fertigation. In addition, the treatment optimal interval fertigation effectively avoided inorganic nitrogen accumulation in soil and significantly (P<0.05) increased the partial factor productivity of applied nitrogen by 88% and 209% in the early-spring and autumn-winter seasons, respectively, when compared to conventional interval fertigation. Although soils under the treatments optimal interval fertigation and optimal daily fertigation received the same amount of fertilizers, the treatment optimal daily fertigation maintained the relatively stable water, electrical conductivity and mineral nitrogen levels in surface soils, promoted fine root (<1.5 mm diameter) growth of cucumber, and eventually increased cucumber economic yield by 6.2% and 8.3% and partial factor productivity of applied nitrogen by 55% and 75% in the early-spring and autumn-winter seasons, respectively, when compared to the treatment optimal interval fertigation. These results suggested that optimal daily fertigation is a beneficial practice for improving crop yield and the water and fertilizers use efficiency in solar greenhouse.