Distribution and functional classification of the 381 SA-responsive DEPs.

(A) The numbers of SA-responsive DEPs that were identified at 12 hpt, 72 hpt or both time points are shown in the Venn diagram. (B) Functional classification and distribution of the DEPs via the GO and KEGG databases. (C) The number of DEPs that were up-regulated or down-regulated is also given for each category. The abbreviation for each functional category is indicated in (B). hpt, hours post treatment.</p

Table_4_Suppression of Cell Tumorigenicity by Non-neural Pro-differentiation Factors via Inhibition of Neural Property in Tumorigenic Cells.xlsx

Our studies have demonstrated that cell tumorigenicity and pluripotent differentiation potential stem from neural stemness or a neural ground state, which is defined by a regulatory network of higher levels of machineries for basic cell physiological functions, including cell cycle, ribosome biogenesis, protein translation, spliceosome, epigenetic modification factors, reprogramming factors, etc., in addition to the neural stemness specific factors. These machineries and neural stemness factors mostly play cancer-promoting roles. It can be deduced that differentiation requires the repression of neural ground state and causes the reduction or loss of neural ground state and thus tumorigenicity in tumorigenic cells. Formerly, we showed that neuronal differentiation led to reduced tumorigenicity in tumorigenic cells. In the present study, we show that non-neural pro-differentiation factors, such as GATA3, HNF4A, HHEX, and FOXA3 that specify mesodermal or/and endodermal tissues during vertebrate embryogenesis, suppress tumorigenicity via repression of neural stemness and promotion of non-neural property in tumorigenic cells. Mechanistically, these transcription factors repress the transcription of neural enriched genes and meanwhile activate genes that specify non-neural properties via direct binding to the promoters of these genes. We also show that combined expression of HHEX and FOXA3 suppresses tumorigenesis effectively in the AOM/DSS model of colitis-associated cancer. We suggest that targeting the property of neural stemness could be an effective strategy for cancer therapy.</p

Time courses of endogenous SA accumulation, <i>PR1-1a</i>and <i>GRXC9</i> expression, and net photosynthetic rate (<i>P</i>_n) in the leaves of cucumber seedlings upon SA treatment.

<p>(A) The contents of endogenous SA, in both free and conjugated forms. (B, C) The relative expression levels of <i>PR1-1a</i> and <i>GRXC9</i>(B) and <i>P</i>_n (C) at different times after SA treatment. The seedlings that were treated without SA were used as controls. Data represent the means of three replicates ± SD.*<i>P</i> < 0.05 and **<i>P</i> < 0.01 compared to the corresponding value from the control.</p

Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

<div><p>Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (<i>Cucumis sativus</i> L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses.</p></div

Table_5_Suppression of Cell Tumorigenicity by Non-neural Pro-differentiation Factors via Inhibition of Neural Property in Tumorigenic Cells.xlsx

Our studies have demonstrated that cell tumorigenicity and pluripotent differentiation potential stem from neural stemness or a neural ground state, which is defined by a regulatory network of higher levels of machineries for basic cell physiological functions, including cell cycle, ribosome biogenesis, protein translation, spliceosome, epigenetic modification factors, reprogramming factors, etc., in addition to the neural stemness specific factors. These machineries and neural stemness factors mostly play cancer-promoting roles. It can be deduced that differentiation requires the repression of neural ground state and causes the reduction or loss of neural ground state and thus tumorigenicity in tumorigenic cells. Formerly, we showed that neuronal differentiation led to reduced tumorigenicity in tumorigenic cells. In the present study, we show that non-neural pro-differentiation factors, such as GATA3, HNF4A, HHEX, and FOXA3 that specify mesodermal or/and endodermal tissues during vertebrate embryogenesis, suppress tumorigenicity via repression of neural stemness and promotion of non-neural property in tumorigenic cells. Mechanistically, these transcription factors repress the transcription of neural enriched genes and meanwhile activate genes that specify non-neural properties via direct binding to the promoters of these genes. We also show that combined expression of HHEX and FOXA3 suppresses tumorigenesis effectively in the AOM/DSS model of colitis-associated cancer. We suggest that targeting the property of neural stemness could be an effective strategy for cancer therapy.</p

Presentation_1_Suppression of Cell Tumorigenicity by Non-neural Pro-differentiation Factors via Inhibition of Neural Property in Tumorigenic Cells.pdf

Our studies have demonstrated that cell tumorigenicity and pluripotent differentiation potential stem from neural stemness or a neural ground state, which is defined by a regulatory network of higher levels of machineries for basic cell physiological functions, including cell cycle, ribosome biogenesis, protein translation, spliceosome, epigenetic modification factors, reprogramming factors, etc., in addition to the neural stemness specific factors. These machineries and neural stemness factors mostly play cancer-promoting roles. It can be deduced that differentiation requires the repression of neural ground state and causes the reduction or loss of neural ground state and thus tumorigenicity in tumorigenic cells. Formerly, we showed that neuronal differentiation led to reduced tumorigenicity in tumorigenic cells. In the present study, we show that non-neural pro-differentiation factors, such as GATA3, HNF4A, HHEX, and FOXA3 that specify mesodermal or/and endodermal tissues during vertebrate embryogenesis, suppress tumorigenicity via repression of neural stemness and promotion of non-neural property in tumorigenic cells. Mechanistically, these transcription factors repress the transcription of neural enriched genes and meanwhile activate genes that specify non-neural properties via direct binding to the promoters of these genes. We also show that combined expression of HHEX and FOXA3 suppresses tumorigenesis effectively in the AOM/DSS model of colitis-associated cancer. We suggest that targeting the property of neural stemness could be an effective strategy for cancer therapy.</p

Table_2_Suppression of Cell Tumorigenicity by Non-neural Pro-differentiation Factors via Inhibition of Neural Property in Tumorigenic Cells.xlsx

Our studies have demonstrated that cell tumorigenicity and pluripotent differentiation potential stem from neural stemness or a neural ground state, which is defined by a regulatory network of higher levels of machineries for basic cell physiological functions, including cell cycle, ribosome biogenesis, protein translation, spliceosome, epigenetic modification factors, reprogramming factors, etc., in addition to the neural stemness specific factors. These machineries and neural stemness factors mostly play cancer-promoting roles. It can be deduced that differentiation requires the repression of neural ground state and causes the reduction or loss of neural ground state and thus tumorigenicity in tumorigenic cells. Formerly, we showed that neuronal differentiation led to reduced tumorigenicity in tumorigenic cells. In the present study, we show that non-neural pro-differentiation factors, such as GATA3, HNF4A, HHEX, and FOXA3 that specify mesodermal or/and endodermal tissues during vertebrate embryogenesis, suppress tumorigenicity via repression of neural stemness and promotion of non-neural property in tumorigenic cells. Mechanistically, these transcription factors repress the transcription of neural enriched genes and meanwhile activate genes that specify non-neural properties via direct binding to the promoters of these genes. We also show that combined expression of HHEX and FOXA3 suppresses tumorigenesis effectively in the AOM/DSS model of colitis-associated cancer. We suggest that targeting the property of neural stemness could be an effective strategy for cancer therapy.</p

Additional file 2 of Repression of lncRNA PART1 attenuates ovarian cancer cell viability, migration and invasion through the miR-503-5p/FOXK1 axis

Additional file 2: Supplementary Figure 2. Flowchart of the interactions among PART1, miR-503-5p, and FOXK1 on OC progression

Comparison of the expression ratios from qRT-PCR (y-axis) and iTRAQ (x-axis) profiling.

<p>Log₂ expression ratios were calculated from SA-treated samples vs control. hpt, hours post treatment. The data represent the means of three replicates.</p

Changes in the H₂O₂ contents in response to SA in the first leaves of cucumber seedlings.

<p>(A) <i>In situ</i> detection of H₂O₂ by DAB staining. (B, C) Quantitative determination of total (B) and chloroplastic (C) H₂O₂ levels under light and dark conditions. The data represent the means of three replicates ± SD. *<i>P</i> < 0.05 and **<i>P</i> < 0.01 compared to the corresponding value from the control.</p