PLAUR facilitates the progression of clear cell renal cell carcinoma by activating the PI3K/AKT/mTOR signaling pathway.

Background: PLAUR has been found upregulated in various tumors and closely correlated with the malignant phenotype of tumor cells. The aim of this study was to investigate the relationship between PLAUR and clear cell renal cell carcinoma (ccRCC) and its potential mechanism of promoting tumor progression. Methods: The expression levels and clinical significance of PLAUR, along with the associated signaling pathways, were extensively investigated in ccRCC samples obtained from The Cancer Genome Atlas (TCGA). PLAUR expression in 20 pairs of ccRCC tumor tissues and the adjacent tissues was assessed using qRT-PCR and IHC staining. Additionally, a series of in vitro experiments were conducted to investigate the impact of PLAUR suppression on cellular proliferation, migration, invasion, cell cycle progression, and apoptosis in ccRCC. The Western blot analysis was employed to investigate the expression levels of pivotal genes associated with the PI3K/AKT/mTOR signaling pathway. Results: The expression of PLAUR was significantly upregulated in ccRCC compared to normal renal tissues, and higher PLAUR expression in ccRCC was associated with a poorer prognosis than low expression. The in-vitro functional investigations demonstrated that knockdown of PLAUR significantly attenuated the proliferation, migration, and invasion capabilities of ccRCC cells. Concurrently, PLAUR knockdown effectively induced cellular apoptosis, modulated the cell cycle, inhibited the EMT process, and attenuated the activation of the PI3K/AKT/mTOR signaling pathway. PLAUR may represent a key mechanism underlying ccRCC progression. Conclusions: The involvement of PLAUR in ccRCC progression may be achieved through the activation of the PI3K/AKT/mTOR signaling pathway, making it a reliable biomarker for the identification and prediction of ccRCC.

Endophytic infection increases the belowground over-yielding effects of the host grass community mainly by increasing the complementary effects.

Introduction: Increases in plant species diversity may increase the community diversity effect and produce community over-yielding. Epichloë endophytes, as symbiotic microorganisms, are also capable of regulating plant communities, but their effects on community diversity effects are often overlooked. Methods: In this experiment, we investigated the effects of endophytes on the diversity effects of host plant community biomass by constructing artificial communities with 1-species monocultures and 2- and 4-species mixtures of endophyte-infected (E+) and endophyte-free (E-) Achnatherum sibiricum and three common plants in its native habitat, which were potted in live and sterilized soil. Results and discussion: The results showed that endophyte infection significantly increased the belowground biomass and abundance of Cleistogenes squarrosa, marginally significantly increased the abundance of Stipa grandis and significantly increased the community diversity (evenness) of the 4-species mixtures. Endophyte infection also significantly increased the over-yielding effects on belowground biomass of the 4-species mixtures in the live soil, and the increase in diversity effects on belowground biomass was mainly due to the endophyte significantly increasing the complementary effects on belowground biomass. The effects of soil microorganisms on the diversity effects on belowground biomass of the 4-species mixtures were mainly derived from their influences on the complementary effects. The effects of endophytes and soil microorganisms on the diversity effects on belowground biomass of the 4-species communities were independent, and both contributed similarly to the complementary effects on belowground biomass. The finding that endophyte infection promotes belowground over-yielding in live soil at higher levels of species diversity suggests that endophytes may be one of the factors contributing to the positive relationship between species diversity and productivity and explains the stable co-existence of endophyte-infected Achnatherum sibiricum with a variety of plants in the Inner Mongolian grasslands.

Infection by Endophytic Epichloë sibirica Was Associated with Activation of Defense Hormone Signal Transduction Pathways and Enhanced Pathogen Resistance in the Grass Achnatherum sibiricum.

Epichloë endophytes can improve the resistance of host grasses to pathogenic fungi, but the underlying mechanisms remain largely unknown. Here, we used phytohormone quantifications, gene expression analysis, and pathogenicity experiments to investigate the effect of Epichloë sibirica on the resistance of Achnatherum sibiricum to Curvularia lunata pathogens. Comparison of gene expression patterns between endophyte-infected and endophyte-free leaves revealed that endophyte infection was associated with significant induction of 1,758 and 765 differentially expressed genes in the host before and after pathogen inoculation, respectively. Functional analysis of the differentially expressed genes suggested that endophyte infection could activate the constitutive resistance of the host by increasing photosynthesis, enhancing the ability to scavenge reactive oxygen species, and actively regulating the expression of genes with function related to disease resistance. We found that endophyte infection was associated with induction of the expression of genes involved in the biosynthesis pathways of jasmonic acid, ethylene, and pipecolic acid and amplified the defense response of the jasmonic acid/ethylene co-regulated EIN/ERF1 transduction pathway and Pip-mediated TGA transduction pathway. Phytohormone quantifications showed that endophyte infection was associated with significant accumulation of jasmonic acid, ethylene, and pipecolic acid after pathogen inoculation. Exogenous phytohormone treatments confirmed that the disease index of plants was negatively related to both jasmonic acid and ethylene concentrations. Our results demonstrate that endophyte infection can not only improve the constitutive resistance of the host to phytopathogens before pathogen inoculation but also be associated with enhanced systemic resistance of the host to necrotrophs after C. lunata inoculation.

Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are essential regulators for various human cancers. However, these lncRNAs need to be further classified for cancer. In the present study, we identified novel competing endogenous RNA (ceRNA) network for bladder cancer (BC) and explored the gene functions of the ceRNA regulatory network. METHODS: Differential gene expression analysis were performed on The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) datasets to identify differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs). Based on the competing endogenous RNA (ceRNA) hypothesis, a lncRNA-miRNA-mRNA network was constructed using the StarBase database and visualization by Cytoscape software. Functional enrichment analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed via R package ClusterProfiler. The protein-protein interaction network was constructed by STRING database and visualization by Cytoscape. Finally, we used CIBERSORT and the TIMER database to analyze the immune infiltrations for BC. RESULTS: The regulatory network was constructed via TCGA BLCA cohort. The differential expressions of lncRNA, miRNA, and mRNA were 186, 200, and 2,661, respectively. There were 106 lncRNA, miRNA, and mRNA included in the ceRNA network. In this network, Calcium Voltage-gated Channel Auxiliary Subunit Alpha2delta1 (CACNA2D1, P<0.001), domain containing engulfment adaptor1 (GULP1, P=0.001), latent transforming growth factor beta binding protein 1 (LTBP1, P=0.006), myosin light chain kinase (MYLK, P=0.001), serpin family E member 2 (SERPINE2, P=0.002), spectrin beta non-erythrocytic 2 (SPTBN2, P=0.047), and hsa-miR-590-3p (P<0.001) significantly affected the prognosis of BC patients. Functional enrichment analyses showed that the biological functions included negative regulation of protein phosphorylation, cell morphogenesis, and sensory organ morphogenesis. Important cancer pathways of KEGG included parathyroid hormone synthesis secretion action, the notch signaling pathway, MAPK signaling pathway, the Rap1 signaling pathway, signaling pathways regulating the pluripotency of stem cells, and the transforming growth factor-ß signaling pathway. Our findings demonstrated that the ceRNA network has important biological functions and a significant influence on the prognosis of BC. CONCLUSIONS: The lncRNA-miRNA-mRNA network constructed in the present study could provide useful insight into the underlying tumorigenesis of BC, and can determine new molecular biomarkers for the diagnosis and therapeutical treatment of BC.

Endophytic Fungi Activated Similar Defense Strategies of Achnatherum sibiricum Host to Different Trophic Types of Pathogens.

It is well documented that Epichloë endophytes can enhance the resistance of grasses to herbivory. However, reports on resistance to pathogenic fungi are limited, and their conclusions are variable. In this study, we chose pathogenic fungi with different trophic types, namely, the biotrophic pathogen Erysiphales species and the necrotrophic pathogen Curvularia lunata, to test the effects of Epichloë on the pathogen resistance of Achnatherum sibiricum. The results showed that, compared to Erysiphales species, C. lunata caused a higher degree of damage and lower photochemical efficiency (Fv/Fm) in endophyte-free (E-) leaves. Endophytes significantly alleviated the damage caused by these two pathogens. The leaf damaged area and Fv/Fm of endophyte-infected (E+) leaves were similar between the two pathogen treatments, indicating that the beneficial effects of endophytes were more significant when hosts were exposed to C. lunata than when they were exposed to Erysiphales species. We found that A. sibiricum initiated jasmonic acid (JA)-related pathways to resist C. lunata but salicylic acid (SA)-related pathways to resist Erysiphales species. Endophytic fungi had no effect on the content of SA but increased the content of JA and total phenolic compounds, which suggest that endophyte infection might enhance the resistance of A. sibiricum to these two different trophic types of pathogens through similar pathways.

Removal of Soil Microbes Alters Interspecific Competitiveness of Epichloë Endophyte-Infected over Endophyte-Free Leymus chinensis.

Epichloë endophytes may not only affect the growth and resistances of host grasses, but may also affect soil environment including soil microbes. Can Epichloë endophyte-mediated modification of soil microbes affect the competitive ability of host grasses? In this study, we tested whether Epichloë endophytes and soil microbes alter intraspecific competition between Epichloë endophyte-colonized (EI) and endophyte-free (EF) Leymus chinensis and interspecific competition between L. chinensis and Stipa krylovii. The results demonstrated that Epichloë endophyte colonization significantly enhanced the intraspecific competitive ability of L. chinensis and that this beneficial effect was not affected by soil microbes. Under interspecific competition, however, significant interactions between Epichloë endophytes and soil microbes were observed. The effect of Epichloë endophytes on interspecific competitiveness of the host changed from positive to neutral with soil microbe removal. Here higher mycorrhizal colonization rates probably contributed to interspecific competitive advantages of EI over EF L. chinensis. Our result suggests that Epichloë endophytes can influence the competitive ability of the host through plant soil feedbacks from the currently competing plant species.

Corrigendum: Endophytic Fungi Activated Similar Defense Strategies of Achnatherum sibiricum Host to Different Trophic Types of Pathogens.

[This corrects the article DOI: 10.3389/fmicb.2020.01607.].

A Functional rs353293 Polymorphism in the Promoter of miR-143/145 Is Associated with a Reduced Risk of Bladder Cancer.

BACKGROUND AND OBJECTIVES: MicroRNA (miR)-143/145, known as tumor suppressors, can promote cell apoptosis and differentiation, and suppress cell proliferation, invasion and migration. We performed a case-control study to investigate the association of rs353293 in the promoter region of miR-143/145 with bladder cancer risk. METHODS: In total, 869 subjects including 333 cases and 536 controls were enrolled in this study, and the rs353293 polymorphism was genotyped by using a Taqman assay. The promoter activity was measured by the Dual-Luciferase Assay System. RESULTS: We calculated an adjusted odds ratio of 0.64 for the presence of either AA/AG genotypes (95% CI 0.46-0.90) and 0.64 (95% CI 0.47-0.87) for carrying at least one A allele in bladder cancer. Stratified analyses showed that the AA/AG genotypes and the A allele were less prevalent in patients with low grade tumors, compared to those harboring higher grade bladder cancers (adjusted OR = 0.53, 95% CI, 0.30-0.94, P = 0.03 and adjusted OR = 0.54, 95% CI, 0.32-0.92, P = 0.02, respectively). In vitro luciferase reporter analysis showed that rs353293A allele had a lower activity compared with the rs353293G allele (P < 0.001). CONCLUSION: These findings suggest that the functional rs353293 polymorphism may be a useful biomarker to predict the risk of bladder cancer.