Arsenic-Hyperaccumulator <i>Pteris vittata</i> Effectively Uses Sparingly-Soluble Phosphate Rock: Rhizosphere Solubilization, Nutrient Improvement, and Arsenic Accumulation

Sparingly-soluble phosphate rock (PR), a raw material for P-fertilizer production, can be effectively utilized by the As-hyperaccumulator Pteris vittata but not most plants. In this study, we investigated the associated mechanisms by measuring dissolved organic carbon (DOC) and acid phosphatase in the rhizosphere, and nutrient uptake and gene expression related to the As metabolism in P. vittata. The plants were grown in a soil containing 200 mg kg–1 As and/or 1.5% PR for 30 days. Compared to the As treatment, the P. vittata biomass was increased by 33% to 4.6 g plant–1 in the As+PR treatment, corresponding to 27% decrease in its frond oxidative stress as measured by malondialdehyde. Due to PR-enhanced DOC production in the rhizosphere, the Ca, P, and As contents in P. vittata fronds were increased by 17% to 9.7 g kg–1, 29% to 5.0 g kg–1, and 57% to 1045 mg kg–1 in the As+PR treatment, thereby supporting its better growth. Besides, PR-induced rhizosphere pH increase from 5.0 to 6.9 promoted greater P uptake by P. vittata probably via upregulating low-affinity P transporters PvPTB1;1/1;2 by 3.7–4.1 folds. Consequently, 29% lower available-P induced the 3.3-fold upregulation of high-affinity P transporter PvPht1;3 in the As+PR treatment, which was probably responsible for the 58% decrease in available-As content in the rhizosphere. Consistent with the enhanced As translocation and sequestration, arsenite antiporters PvACR3/3;3 were upregulated by 1.8–4.4 folds in the As+PR than As treatment. In short, sparingly-soluble PR enhanced the Ca, P, and As availability in P. vittata rhizosphere and improved their uptake via upregulating genes related to As metabolism, suggesting its potential application for improving phytoremediation in As-contaminated soils

DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing

Abstract DIS3-like 3′-5′ exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored. Here, aberrant DIS3L2 expression promoted human hepatocellular carcinoma (HCC) progression via heterogeneous nuclear ribonucleoproteins (hnRNP) U-mediated alternative splicing. DIS3L2 directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1 independent of its exonuclease activity, yielding an oncogenic splicing variant, Rac1b, which is known to stimulate cellular transformation and tumorigenesis. DIS3L2 regulated alternative splicing by recruiting hnRNP U to pre-Rac1. Rac1b was critical for DIS3L2 promotion of liver cancer development both in vitro and in vivo. Importantly, DIS3L2 and Rac1b expression highly correlated with HCC progression and patient survival. Taken together, our findings uncover an oncogenic role of DIS3L2, in which it promotes liver cancer progression through a previously unappreciated mechanism of regulating hnRNP U-mediated alterative splicing. Significance: These findings establish the role and mechanism of the 3′-5′ exoribonuclease DIS3L2 in hepatocellular carcinoma carcinogenesis. </jats:sec

Polo-like kinase 1 coordinates biosynthesis during cell cycle progression by directly activating pentose phosphate pathway

Polo-like kinase 1 (Plk1) is a key regulator of mitosis. Here, the authors show that Plk1 activates the pentose phosphate pathway in cancer cells by directly phosphorylating glucose-6-phosphate dehydrogenase (G6PD) and that such activation is critical for cell cycle progression and cancer cell growth

IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis

AbstractDiffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.</jats:p

Supplementary Figure S1-S5, and Tables S1-S8 from DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing

Supplementary Figures: SF1, DIS3L2 promotes cell growth in Hep3B and HepG2 cells. SF2, DIS3L2 interacts hnRNP U in Hep3B and HepG2 hepatocellular carcinoma cells. SF3, DIS3L2 and hnRNP U promote exon 3b inclusion during pre-Rac1 splicing. SF14, The effect of knockdown of pre-Rac1. SF5, DIS3L2 promotes HCC growth via Rac1b. Supplementary Tables: Table S1, clinicopathological characteristics of clinical samples. Table S2, the expression of DIS3L2 in relation to clinicopathological characteristics of liver cancer patients by the chi-square test. Table S3, the correlation between DIS3L2 and clinicopathological characteristics of clinical samples by Spearman analysis. Table S4, Univariate analysis and multivariate analyses of parameters associated with overall survival of HCC patients. Table S5-S7, Nucleotide sequences of primers used for semi-RT-PCR, RIP assays, quantitative real-time RT-PCR. Table S8, Sequences of the oligonucleotides for shRNA.</p