Anillin contributes to prostate cancer progression through the regulation of IGF2BP1 to promote c-Myc and MAPK signaling.

Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. Anillin (ANLN) is an actin-binding protein that is involved in various malignancies, including PCa. However, the regulatory mechanism of ANLN in PCa remains unclear. Exploring the role of ANLN in PCa development and discovering novel therapeutic targets are crucial for PCa therapy. In the current work, we discovered that ANLN expression was considerably elevated in PCa tissues and cell lines when compared to nearby noncancerous prostate tissues and normal prostate epithelial cells. ANLN was associated with more advanced T stage, N stage, higher Gleason score, and prostate-specific antigen (PSA) level. In addition, we discovered that overexpression of ANLN promoted PCa cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, we performed RNA-seq to identify the regulatory influence of ANLN on the MAPK signal pathway. Furthermore, a favorable association between ANLN expression and IGF2BP1 expression was identified. The tumor-suppressive impact of ANLN downregulation on PCa cell growth was partially reversed by overexpressing IGF2BP1. Meanwhile, we discovered that ANLN can stabilize the proto-oncogene c-Myc and activate the MAPK signaling pathway through IGF2BP1. These findings indicate that ANLN could be a potential therapeutic target in PCa.

CircUBE3A(2,3,4,5) promotes adenylate-uridylate-rich binding factor 1 nuclear translocation to suppress prostate cancer metastasis.

Metastatic progression is the primary cause of mortality in prostate cancer (PCa) patients. Although circular RNAs (circRNAs) have been implicated in cancer progression and metastasis, our current understanding of their role in PCa metastasis remains limited. In this study, we identified that circUBE3A(2,3,4,5), which originated from exons 2, 3, 4 and 5 of the human ubiquitin-protein ligase E3A (UBE3A) gene, was specifically downregulated in PCa tissues and correlated with the Gleason score, bone metastasis, and D'Amico risk classification. Through the in vitro and in vivo experiments, we demonstrated that overexpression of circUBE3A(2,3,4,5) inhibited PCa cell migration, invasion, metastasis, and proliferation. Mechanistically, circUBE3A(2,3,4,5) was found to bind to adenylate-uridylate-rich binding factor 1 (AUF1), promoting the translocation of AUF1 into the nucleus. This led to decreased AUF1 in the cytoplasm, resulting in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) mRNA instability and a subsequent reduction at the protein level. The downregulation of MTHFD2 further inhibited vimentin expression, thereby suppressing PCa cell epithelial-mesenchymal transition. Additionally, two pairs of the short-inverted repeats (TSIRs) in flanking introns were identified to synergistically facilitate the generation of circUBE3A(2,3,4,5) and other circRNAs. In summary, TSIRs-induced circUBE3A(2,3,4,5) acts as a suppressor of PCa metastasis by enhancing AUF1 nuclear translocation, reducing MTHFD2, and subsequently inhibiting vimentin expression. This study characterizes circUBE3A(2,3,4,5) as a functional circRNA and proposes it as a highly promising target for preventing PCa metastasis.

Effect of damming on hydrogeochemical characteristics and potential environmental risks in a large reservoir: Insights from different vertical layer sampling.

The water environment of large reservoirs is fragility due to effects from hydrological regulation of damming and anthropogenic inputs. As a critical path to quantify the natural chemical weathering and assess environmental risks, solute chemistry of river has been widely focused on. However, the complexed hydrological conditions of large reservoir affect the chemical compositions, and the significance of solute vertical geochemistry as an indicator of chemical weathering and water quality health remains explore. Therefore, the Three Gorges Reservoir (TGR) was selected as a typical study area, which is the world's largest hydropower project and subject to frequent water quality problems. Then, the chemical compositions in stratified water were determined. Ca2+ (52.8 ± 4.3 mg/L) and HCO3- (180.9 ± 8.9 mg/L) were the most abundant ions among cations and anions, respectively. Incremental mean concentration of total major ions followed with the increase of riverine depth and flow direction. An improved inversion model was used to quantify the source contribution, which weathering of dolomite (34%) and calcite (38%) contributed the most to total cations, and the influences of agriculture and sewage discharge were limited. Additional contributions of evaporite and pyrite oxidation were found in analysis of deeper water samples, which also results in 2%-67% difference in estimated CO2 release flux using data from different depth, indicating additional information about sulfuric acid driven weathering was contained. Finally, the water quality of the reservoir was assessed for irrigation and non-carcinogenic risks. Results showed the stratified water of TGR can be used as a good water source of irrigation. However, NO3- (5.1 ± 1.1 mg/L) may have a potential non-carcinogenic risk to children, especially in surface water. To sum up, this study provided an indispensable supplement to the water chemistry archives in the TGR basin, serving as theoretical references for environmental management of large reservoirs.

The short inverted repeats-induced circEXOC6B inhibits prostate cancer metastasis by enhancing the binding of RBMS1 and HuR.

Circular RNAs (circRNAs) are a novel class of endogenous RNAs with a covalently closed loop structure. Many circRNAs have been found to participate in cancer progression. However, the detailed generation process, functions, and related mechanisms of circRNAs in prostate cancer (PCa) remain largely unknown. In the present study, we identified circEXOC6B, a novel suppressor in the metastasis of PCa. Functionally, circEXOC6B, originating from the exocyst complex component 6B (EXOC6B) gene, inhibited migration and invasion of PCa in vitro and in vivo. Mechanistically, by acting as a protein scaffold, circEXOC6B enhanced the binding of human RNA binding motif single strand interacting protein 1 (RBMS1) and human antigen R (HuR) and further increased A-kinase anchoring protein 12 (AKAP12) expression to inhibit PCa metastasis. Unlike previous studies, we found that one pair of short inverted repeats in flanking introns at least partly promoted the circularization of circEXOC6B. Our study presents a novel mechanism for the inhibitory role of circEXOC6B in PCa metastasis and provides new insight into the molecular process of circRNA generation.

Deep Learning-Based Multi-Omics Integration Robustly Predicts Relapse in Prostate Cancer.

Objective: Post-operative biochemical relapse (BCR) continues to occur in a significant percentage of patients with localized prostate cancer (PCa). Current stratification methods are not adequate to identify high-risk patients. The present study exploits the ability of deep learning (DL) algorithms using the H2O package to combine multi-omics data to resolve this problem. Methods: Five-omics data from 417 PCa patients from The Cancer Genome Atlas (TCGA) were used to construct the DL-based, relapse-sensitive model. Among them, 265 (63.5%) individuals experienced BCR. Five additional independent validation sets were applied to assess its predictive robustness. Bioinformatics analyses of two relapse-associated subgroups were then performed for identification of differentially expressed genes (DEGs), enriched pathway analysis, copy number analysis and immune cell infiltration analysis. Results: The DL-based model, with a significant difference (P = 6e-9) between two subgroups and good concordance index (C-index = 0.767), were proven to be robust by external validation. 1530 DEGs including 678 up- and 852 down-regulated genes were identified in the high-risk subgroup S2 compared with the low-risk subgroup S1. Enrichment analyses found five hallmark gene sets were up-regulated while 13 were down-regulated. Then, we found that DNA damage repair pathways were significantly enriched in the S2 subgroup. CNV analysis showed that 30.18% of genes were significantly up-regulated and gene amplification on chromosomes 7 and 8 was significantly elevated in the S2 subgroup. Moreover, enrichment analysis revealed that some DEGs and pathways were associated with immunity. Three tumor-infiltrating immune cell (TIIC) groups with a higher proportion in the S2 subgroup (p = 1e-05, p = 8.7e-06, p = 0.00014) and one TIIC group with a higher proportion in the S1 subgroup (P = 1.3e-06) were identified. Conclusion: We developed a novel, robust classification for understanding PCa relapse. This study validated the effectiveness of deep learning technique in prognosis prediction, and the method may benefit patients and prevent relapse by improving early detection and advancing early intervention.

Enhancement of Lignin Extraction of Poplar by Treatment of Deep Eutectic Solvent with Low Halogen Content.

A novel choline-based deep eutectic solvent (DES) with low halogen content-namely choline lactate-lactic acid (CLL)-was synthesized by replacing the chloride anion with lactate anion in choline chloride-lactic acid (CCL). CLL and CCL treatments were conducted at 140 °C for 12 h with hydrogen bond acceptor/hydrogen bond donor =1/10, thereafter composition analysis and characterizations of the lignin extracted by DES treatment (DES lignin) and the solid residue were carried out. The proposed low halogen content DES presented an improved lignin extraction efficiency. The CLL treatment extracted 90.13% of initial lignin from poplar, while CCL extracted 86.02%. In addition, the CLL treatment also provided DES lignin with an improved purity (91.17%), lower molecular weight (Mw/Mn=1805/971 g/mol) and more concentrated distribution (polydispersity index=1.86). The efficient lignin extraction was mainly ascribed to the cleavage of ß-O-4 bonds in lignin macromolecule, especially in the guaiacyl units, thereby breaking them into smaller molecules, facilitating the lignin extraction. The replacement of chloride anion allowed CLL acting as a more efficient DES to interact with lignin macromolecules, thus providing lignin with higher uniformity and suitable molecular weight. The low halogen content DES system proposed in present work could benefit the fractionation of biomass, improve the valorization of lignin compounds and facilitate industrial process in the downstream.

Fe, Rather Than Soil Organic Matter, as a Controlling Factor of Hg Distribution in Subsurface Forest Soil in an Iron Mining Area.

To identify whether the iron (Fe) mining area in the Jiulongjiang River basin (JRB) has an influence on the mercury in the forest soil, the spatial distribution patterns of mercury's behavior on different controlling factors were analyzed, and a potential ecological risk assessment was done. A total of 107 soil samples were collected from two forest soil profiles, one profile near the Fe mining area and the other far from it. The soil near the mining area had a moderate potential ecological risk with high Fe content rich in the upper layer of soil (<70 cm), whereas soil collected far from the mining area had a low potential ecological risk. These results indicated that the rise of iron content in the soil near the mining area was beneficial to the enrichment of mercury, probably causing damage to the forest ecosystem. Both soil organic carbon (SOC) and Fe content have strong positive correlations with THg content, controlling the mercury behavior in the upper layer (<70 cm) and a lower layer (>70 cm) of soil, respectively. The high Fe content in the upper layer of soil will compete for the adsorption of mercury by SOC, leading to the poor correlation between SOC and THg.