Search

Constitutive ERK1/2 activation has been frequently observed in pancreatic adenocarcinoma (PDAC). How ERK1/2 activation status been potentiated and maintained by epigenetic mechanisms has seldom been discussed in PDAC. In this study, we first examined the expression status of p-ERK1/2 in PDAC tissues by immunohistochemical staining and then screened possible epigenetic factors that displayed different expression status between p-ERK1/2 high and low groups by RNA profiling, and found that SETD8 displayed an increased expressional pattern in p-ERK1/2high patient group. Then the impact of SETD8 on the proliferation of PDAC cells were investigated on the basis of gain or loss-of-function assays. RNA sequencing assays were performed to screen potential SETD8 downstream targets that contribute to ERK1/2 activation. Mass spectrometry and transcriptional analysis, including dual-luciferase assay and chromatin immunoprecipitation assay (ChIP), were used to explore the molecular mechanisms that governing SETD8-mediated ERK1/2 activation. In vitro cell line studies and in vivo xenograft mouse model studies indicated that SETD8 promoted cell proliferation and increased tumor formation capacity of PDAC cell lines. Mechanism explorations uncovered that SETD8 suppressed the expression of DUSP10, which was responsible for dephosphorylation of ERK1/2. Mass spectrometry and transcriptional analysis results demonstrated that STAT3 interacted with SETD8 and recruited SETD8 to the promoter region of DUSP10, leading to epigenetic silencing of DUSP10 and the resultant activation of ERK1/2. In conclusion, SETD8 interacts with STAT3 on DUSP10 promoter region and epigenetically silences DUSP10 expression. Decreased DUSP10 expression in PDAC potentiates activation of ERK1/2 phosphorylation, resulting in unfavorable prognosis of PDAC.

A quantitative comparative analysis of PM accumulation on boles, branches and leaves is necessary to better understand the reduction of airborne PM by trees. This study compared the total water-insoluble particle accumulation mass per unit area, the distribution of water-insoluble particle size fractions, and the accumulation masses and compositions of water-soluble ions among different vegetative organs. The average accumulation capacity of water-insoluble particles was as follows: leaf epicuticular wax (11.1 ± 4.4 μg/cm2), leaf surfaces (22.0 ± 3.2 μg/cm2), terminal branch surfaces (101.6 ± 47.0 μg/cm2), perennial branch surfaces (92.7 ± 20.0 μg/cm2), and bark surfaces (1719.9 ± 684.7 μg/cm2). Bole bark surfaces tended to accumulate the largest proportion of large particles, averaging 88 ± 4%. Branch surfaces and leaf epicuticular wax accumulated the largest proportions of fine particles, averaging 15 ± 5%. The total masses of water-soluble ions were 18 ± 10%, 33 ± 13% and 32 ± 6% of the total water-insoluble particles on boles, terminal branches and leaves, respectively. Leaf surfaces accumulated 2.2–6.0 times more SO2- 4 and NO 3 than did branch and bark surfaces.

FBW7 functions as a tumor suppressor by targeting oncoproteins for degradation. Our previous study found FBW7 was low expressed in pancreatic cancer due to sustained activation of Ras-Raf-MEK-ERK pathway, which destabilized FBW7 by phosphorylating at Thr205. MicroPET/CT imaging results revealed that FBW7 substantially decreased 18F-fluorodeoxyglucose uptake in xenograft tumors. Mechanistically, FBW7 inhibited glucose metabolism via c-Myc/TXNIP axis. But in these studies, we observed FBW7 down-regulated genes were widely involved in redox reaction and lipid metabolism. Here we reanalyzed previous gene expression profiling and conducted targeted cell metabolites analysis. Results revealed that FBW7 regulated lipid peroxidation and promoted ferroptosis, a non-apoptotic form of cell death. Mechanistically, we found FBW7 inhibited the expression of stearoyl-CoA desaturase (SCD1) via inhibiting nuclear receptor subfamily 4 group A member 1 (NR4A1). SCD1 was reported to inhibit both ferroptosis and apoptosis, which was consistent with the function of FBW7 and NR4A1, another FBW7 down-regulated gene in the gene expression profiling. Moreover, FBW7 potentiated cytotoxic effect of gemcitabine via activating ferroptosis and apoptosis. Combination ferroptosis inducers and apoptosis activators could also significantly potentiated cytotoxic effect of gemcitabine in pancreatic cancer. Therefore, our findings might provide new strategies for the comprehensive treatment of pancreatic cancer., Graphical abstract Image 1, Highlights • Ferroptosis possesses great potential in pancreatic cancer therapy. • FBW7 synchronously induces apoptosis and ferroptosis. • Activation of apoptosis and ferroptosis potentiates cytotoxic effect of gemcitabine.

The presence of plant leaves has been shown to lower the risks of health problems by reducing atmospheric particulate matter (PM). Leaf PM accumulation capacity will saturate in the absence of runoff. Rainfall is an effective way for PM to “wash off” into the soil and renew leaf PM accumulation. However, little is known about how PM wash-off varies with PM size and health problems caused by particulate pollution vary with PM size. This study thus used artificial rainfall with six plant species to find out how size-fractioned PM are washed off during rain processes. Total wash-off masses in fine, coarse and large fractions were 0.6–10.3 μg/cm2, 1.0–18.8 μg/cm2 and 4.5–60.1 μg/cm2 respectively. P. orientalis (cypress) and E. japonicus (evergreen broadleaved shrub) had the largest wash-off masses in each fraction during rainfall. P. cerasifera (deciduous broadleaved shrub) had the largest cumulative wash-off rates in each fraction. Rainfall intensity had more influence on wash-off masses and rates of large particles for six species and for small particles in evergreen species, but limited effect on wash-off proportions. Wash-off proportions decreased in large particles and increased in small particles along with rainfall. The results provide information for PM accumulation renewal of plants used for urban greening.