CircGLIS3 inhibits thyroid cancer invasion and metastasis through miR-146b-3p/AIF1L axis.

PURPOSE: Studies have shown that circRNA is involved in the occurrence and development of human cancers. However, it remains unclear that the contribution of circRNA in thyroid carcinoma and its role in the process of tumorigenesis. METHODS: The expression profile of circRNA-miRNA-mRNA in thyroid carcinoma was detected by RNA sequencing and verified by qRT-PCR. The characteristics of circGLIS3 were verified by RNase R and actinomycin assays, subcellular fractionation, and fluorescence in situ hybridization. The functions of circGLIS3 and AIF1L were detected by wound healing, transwell, 3D culture and Western blot. RNA Immunoprecipitation (RIP), RNA pulldown and dual-luciferase reporter assays were used to verify the target genes of circGLIS3 and downstream miRNAs. Functional rescue experiments were performed by transfecting miRNA mimics or siRNA of target genes. Finally, metastatic mouse models were used to investigate circGLIS3 function in vivo. RESULTS: In this study, we discovered a novel circRNA (has_circ_0007368, named as circGLIS3) by RNA sequencing. CircGLIS3 was down-regulated in thyroid carcinoma tissues and cells line, and was negatively associated with malignant clinical features of thyroid carcinoma. Functional studies found that circGLIS3 could inhibit the migration and invasion of thyroid carcinoma cells, and was related to the EMT process. Mechanistically, circGLIS3 can upregulate the expression of the AIF1L gene by acting as a miR-146b-3p sponge to inhibit the progression of thyroid carcinoma. CONCLUSION: Our study identified circGLIS3 as a novel tumor suppressor in thyroid cancer, indicating the potential of circGLIS3 as a promising diagnostic and prognostic marker for thyroid cancer.

"Water-Carbon" redistribution caused by China's interprovincial grain transportation.

Water resource and carbon emission involved in grain production in mainland China are redistributed among provinces as the grain was transported in recent years. This study first calculated the water consumption and carbon emission during the growth of grain crops based on the water-carbon footprint theory, and then used the social-equity method to calculate the inter-regional grain virtual water and virtual carbon flow. Finally, the regional and national trends in water saving and carbon emission reduction were calculated based on the spatial and temporal differences in grain planting among provinces. In terms of virtual water-carbon, from 2000 to 2017, the amount of the inter-provincial grain virtual water flow increased from 717.4 × 108 m3 to 1472.6 × 108 m3. Heilongjiang and Guangdong are the provinces with the largest amount of grain virtual water outflow (670.9 × 108 m3) and inflow (402.8 × 108 m3) in 2017, respectively. And the total inter-provincial grain virtual carbon flow increased from 2362.7 × 104 t CO2e to 12,680.6 × 104 t CO2e. Grain transport leads to water saving and carbon emission reduction, the amount of water saving increased from 25.6 × 108 m3 to 77.0 × 108 m3 and the carbon emission reduction increased from 2.4 × 104 t CO2e to 847.4 × 104 t CO2e from 2000 to 2017. Based on research results and from the perspective of socio-hydrology combined with water saving and carbon emission reduction, the regions could optimize the integration of water saving, carbon emission reduction, and sustainable development based on coordinating the grain planting structure according to their own climatic condition, soil and water resource condition, and socioeconomic condition.

[Effects of regulation measure on soil and microbial biomass of moderately degraded alpine meadow in Qilian Mountain, China]. / 调控措施对祁连山中度退化高寒草甸土壤的影响.

We examined the effects of different regulation measures (spring rest grazing, spring rest grazing-cutting turf, spring rest grazing-cutting turf-fertilization, spring rest grazing-cutting turf-sowing, spring rest grazing-cutting turf-fertilization-sowing) on vegetation, soil physical and chemical properties, and soil microbial biomass in mode-rately degraded alpine meadow in Qilian Mountain. The results showed that all the regulation measures significantly increased plant coverage and aboveground and underground biomass of degraded alpine meadows. Plant species richness increased significantly under the two measures of spring rest grazing-cutting turf-fertilization and spring rest grazing-cutting turf-fertilization-sowing. The dominant species of spring rest grazing-cutting turf-sowing and spring rest grazing-cutting turf-fertilization-sowing was Poa pratensis cv. Qinghai. Soil pH and bulk density in moderately degraded alpine meadow (control) were significantly higher than those of all regulation measures. Soil water content, soil organic carbon, total nitrogen and total potassium, carbon-nitrogen ratio and nitrogen-phosphorus ratio of spring rest grazing-cutting turf-fertilization-sowing measures were the highest, which were 21.3%, 22.30 g·kg-1, 2.77 g·kg-1, 19.93 g·kg-1, 8.3 and 3.5, respectively. Soil microbial biomass nitrogen and phosphorus (104.98 and 40.74 mg·kg-1) of degraded meadows under spring rest grazing-cutting turf-fertilization-sowing measures were significantly higher than those of other measures, while soil microbial biomass carbon (240.72 mg·kg-1) of degraded meadows under spring rest grazing-cutting turf-fertilization measures was significantly higher than that of other measures. The results of radar map showed that the regulation measures affected the characteristics of degra-ded meadow vegetation (aboveground and underground biomass), soil physical and chemical properties (water content, organic carbon, total nitrogen, total phosphorus, and total potassium) and soil microbial biomass (carbon, nitrogen and phosphorus). Spring rest grazing-cutting turf-fertilization-sowing measures had the best performance in restoraing degraded meadows in the study area.

Water-Food-Carbon Nexus Related to the Producer-Consumer Link: A Review.

Clarifying the water-food-carbon nexus is key to promoting the harmonious development of human society and environmental resources. The sustainable development of agricultural production systems is being challenged by water scarcity and climate change. Crop growth and irrigation consume large amounts of water, and greenhouse gases are generated due to processes such as fertilizer application and enteric fermentation. These environmental impacts accompany the agricultural production process and are thus embedded in the entire life cycle of diverse food items; in turn, consumers' food choices indirectly impact water consumption and greenhouse gas emissions. Reducing agricultural water consumption and greenhouse gas emissions during food production have become crucial issues in mitigating the projected water, climate, and food crises. From the consumer's perspective, diets vary regionally due to different natural conditions for food production and varying socioeconomic and income levels. This review delves into the interactions between diet and its potential environmental impacts, including water consumption and greenhouse gas emissions, in order to support further development of the water-food-carbon nexus.

The characteristics of soil fungal community in degraded alpine meadow in the Three Rivers Source Region, China.

To clarify the variation of species composition, diversity, and functional structure of soil fungi community along alpine meadow degradation,we examined the characteristics and controlling factors of soil fungal communities in non-degraded, lightly degraded, moderately degraded, severely degraded and extremely degraded (black soil beach) alpine meadows at the Three Rivers Source Region, based on the high-throughput gene sequencing and FUNGuild functional prediction. The results showed that the dominant phyla in alpine meadow soil were Ascomycota, Basidiomycetes, and Mortierellomycota. Species composition of soil fungal community varied greatly in alpine meadow under different levels of degradation. The abundance of Cladosporium flabelliforme, Entoloma sodale, Hygrocybe conica, Inocybe sp. and Trichocladium opacum increased, while that of Gibberella tricincta and Dactylonectria macrodidyma decreased following grassland degradation. The meadow under severe degradation had higher soil fungal Chao1 index, while that under light degradation had lower Shannon index and Simpson index. The abundance of pathologic, symbiotic, and saprophytic types of fungi varied among different alpine meadows. Along with the grassland degradation, the abundance of soil symbiotic fungi decreased, while that of pathological fungi increased. The soil fungal community and functional compositions changed obviously with degradation in the alpine meadow. Plant aboveground biomass, soil water content, pH, total organic carbon, total nitrogen, ammonium nitrogen, available phosphate, total potassium and AN/AP (ratio of available nitrogen and available phosphorus) were the main driving factors for the variations in soil fungal community structure.

Genetic alterations in cfDNA of benign and malignant thyroid nodules based on amplicon-based next-generation sequencing.

BACKGROUND: Circulating cell-free DNA (cfDNA) serves as a biomarker in multiple malignant diseases. However, controversy still surrounds the role of cfDNA detection in the diagnosis and monitoring of papillary thyroid carcinoma (PTC). This study set out to identify the role of cfDNA detection in distinguishing between benign and malignant thyroid nodules. METHODS: Tissue, blood cell, and plasma samples were collected from 10 patients with benign nodules and 10 patients with malignant nodules. The DNA isolated from these samples was subject to PCR-based amplification using primers designed for 50 proto-oncogenes and tumor suppressor genes. PCR products were sequenced using Illumina technology, and the mutations were detected with varScan among sequencing data for each sample and comparative analysis was carried out. RESULTS: Through amplicon sequencing, we found one non-synonymous somatic mutation in the benign nodules and three in the malignant nodules. Among these four mutations, BRAFV600E mutation was detected in the tissue samples of 8 out of the 10 PTC patients, but it was not detected in the benign nodules. However, no BRAFV600E mutation was detected in cfDNA. Further differential analysis of cfDNA indicated that some genes had more mutations in benign patients than in malignant patients, such as MET and IDH, and some genes had more mutations in malignant patients, such as PIK3CA and EZH2. CONCLUSIONS: We found that BRAFV600E mutation was a credible disease-related mutation in PTC; however, it could not be detected in cfDNA. Moreover, there was a large difference in mutation gene distribution between benign and malignant thyroid nodules.

Effects of Stellera chamaejasme removal on the nutrient stoichiometry of S. chamaejasme-dominated grasslands in the Qinghai-Tibetan plateau.

BACKGROUND: Stoichiometric relations drive powerful constraints in several fundamental ecosystem processes. However, limited studies have been conducted on the ecological stoichiometry of plants after the change of community composition induced by Stellera chamaejasme removal in alpine grassland in the Qinghai-Tibetan Plateau. METHODS: We investigated the effects of S. chamaejasme removal on ecological stoichiometry by estimating the C:N:P stoichiometry in species, functional group and community levels of the ecosystem. The interactions between different species, functional groups and correlation with soil nutrient, responding to S. chamaejasme removal were also analyzed. RESULTS: For the plants that became dominant after S. chamaejasme removal (SR), N content decreased and their C:N increased. S. chamaejasme removal significantly affected the nutrient stoichiometry of different functional groups. Specifically, Gramineae in the SR sites had decreased N content and N:P, and increased C:N; however, forbs had increased N content, C:P and N:P and decreased P content and C:N. At the community level, N content was lower and C:N higher in SR communities compared to CK. The N content of the plant community was positively correlated with soil total N content. S. chamaejasme removal could change the nutrient balance from species level, to functional group level, and to community level. Thus, supplementary measures might be cooperated with S. chamaejasme removal for the recovery of S. chamaejasme-dominated degraded grassland. These results provide insight into the role of S. chamaejasme in ecological protection and conservation, and the conclusions from this study could be used to develop effective and sustainable measures for S. chamaejasme control in the Qinghai-Tibetan Plateau.

TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion.

BACKGROUND: Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) promoting demethylation in cells. However, the expression pattern and biologic significance of TET in papillary thyroid carcinoma (PTC) remain unclear. This study aimed to elucidate the biological functions of TET1 and the miRNA and mRNA expression levels in PTC cells with downregulated TET1. METHODS: The expression of the TET family in 49 PTC tissues and corresponding tumor-adjacent tissues, as well as PTC cell lines (BCPAP, K1, and TPC-1) and the normal thyroid epithelial cell line (Nthy-ori 3-1), were detected using quantitative real-time polymerase chain reaction. The 5hmC level was detected in PTC tissues and cell lines using immunohistochemistry and dot blot assay, respectively. After silencing the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. RESULTS: The expression level of TET1 decreased in PTC tissues and cell lines and was consistent with the reduction in the 5hmC level. The knockdown of the TET1 gene with siRNAs in BCPAP and TPC-1 cells, cell proliferation was detected using EdU assay. Transwell assay was used to investigate cell migration and invasion. miRNA and mRNA expression arrays were conducted in TET1-depleted BCPAP cells. WNT4, FZD4, CDK6, MCF2L, and EDN1 was upregulated as potential target genes of dysregulated miRNAs. CONCLUSION: The study showed that TET1 dysfunction inhibited the migration and invasion of BCPAP cells and might have a potential role in the pathogenesis of PTC.

MicroRNA-222 Promotes Invasion and Metastasis of Papillary Thyroid Cancer Through Targeting Protein Phosphatase 2 Regulatory Subunit B Alpha Expression.

BACKGROUND: Increasing evidence indicates that microRNA dysfunction is involved in the pathogenesis and progression of cancer. MicroRNA-222 (miR-222) is upregulated in papillary thyroid carcinoma (PTC). However, the role of miR-222 in invasion and metastasis of PTC remains unknown. This study investigated the function of miR-222 and its underlying mechanism in the progression of PTC. METHODS: The expression of miR-222 was detected by quantitative reverse transcription polymerase chain reaction, and its correlation with various clinical characteristics was analyzed. The role of miR-222 in PTC cell migration ability was assessed with Transwell® assays and wound-healing assays in both TPC-1 and K1 cells. By using bioinformatics analyses and dual-luciferase 3'-UTR reporter assays, the study identified the direct target of miR-222 and the downstream pathways of PTC. Further, the study confirmed the role of miR-222 in promoting PTC distant metastasis in vivo by injecting TPC-1 cells into nude mice. RESULTS: This study confirmed that miR-222 was upregulated in PTC tissues compared to adjacent thyroid tissues and that it correlated with aggressive cancer phenotypes. The results indicate that ectopic miR-222 enhanced cell migration and invasion of thyroid cancer cells in vitro and distant pulmonary metastases in vivo. Protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), a tumor suppressor, was identified as a direct target of miR-222 through the 3'-UTR of PPP2R2A. Restoring PPP2R2A expression led to the attenuation of migration and invasion in miR-222-overexpressing thyroid cancer cells. Moreover, we found that miR-222 promoted invasion and metastasis partly through the AKT signaling pathway. CONCLUSIONS: Taken together, the results suggest that miR-222 promotes tumor invasion and metastasis in thyroid cancer by targeting PPP2R2A. Thus, miR-222 could serve as a potential diagnostic biomarker, as well as an attractive therapeutic tool for thyroid cancer.

MiR-195 Inhibits Tumor Growth and Metastasis in Papillary Thyroid Carcinoma Cell Lines by Targeting CCND1 and FGF2.

BACKGROUND: MicroRNA (miRNA) dysregulation was commonly seen in papillary thyroid carcinoma (PTC), and miR-195 was verified to be downregulated in PTC by the large data set analysis from The Cancer Genome Atlas (TCGA). Our study aimed to explore the biological functions and the underlying molecular mechanisms of miR-195 in PTC. METHODS: The relative expression of miR-195 and its target genes were assessed by quantitative RT-PCR assay in 38 pairs of PTC and the adjacent thyroid tissues. Assays were performed to evaluate the effect of miR-195 on the proliferation, migration, and invasion in PTC cell lines. Moreover, we searched for targets of miR-195 and explored the possible molecular pathway of miR-195 in PTC. RESULTS: We found that miR-195 was downregulated in PTC cell lines and tissues. Overexpression of miR-195 significantly inhibited cell proliferation, migration, and invasion in K1 and BCPAP cell lines. CCND1 and FGF2, which had inverse correlations with miR-195 in clinical specimens, were found to be the direct targets of miR-195. Furthermore, miR-195 might be involved in PTC tumorigenesis by suppressing the Wnt/ß-catenin signaling pathway. CONCLUSIONS: These results highlight an important role of miR-195 in the initiation and progression of PTC and implicate the potential application of miR-195 in PTC target therapy.

MiR-20b Displays Tumor-Suppressor Functions in Papillary Thyroid Carcinoma by Regulating the MAPK/ERK Signaling Pathway.

BACKGROUND: MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs that play important roles in multiple biological processes. MiR-20b has been reported to be dysregulated in papillary thyroid carcinoma (PTC). However, the functional roles are still largely unknown. This study aimed to investigate the biological functions and the underlying molecular mechanisms of miR-20b in PTC. METHOD: The expression of miR-20b was assessed by quantitative reverse transcription polymerase chain reaction in 47 pairs of PTC and adjacent normal thyroid tissues. The association between miR-20b expression and clinicopathologic status of PTC patients was analyzed. MiR-20b was overexpressed in the PTC cell lines K1 and TPC-1, and the effects on cell viability, migration, and invasion were evaluated. The study further searched for targets of miR-20b, and identified the possible molecular mechanisms of miR-20b in PTC cells. Additionally, the effect of miR-20b on tumor growth in nude mice was assessed. RESULTS: It was found that miR-20b was markedly downregulated in PTC tissues compared with their adjacent normal thyroid tissues. The low-level expression of miR-20b was correlated with cervical lymph node metastasis and TNM staging. Upregulation of miR-20b inhibited cell viability, migration, and invasion in K1 and TPC-1 cells. Ectopic overexpression of miR-20b could suppress the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway through directly targeting son of sevenless homolog 1 (SOS1) and extracellular signal-regulated kinase 2 (ERK2). Furthermore, depletion of SOS1 or ERK2 by siRNAs has similar effects as miR-20b overexpression on cell viability and invasion, whereas rescued SOS1 or ERK2 expression partially reversed the inhibitory effects of miR-20b in TPC cell lines. In xenograft animal experiments, it was found that overexpressed miR-20b could suppress tumor growth of PTC cells. CONCLUSION: These results indicate for the first time that miR-20b displays tumor-suppressor functions in PTC. By targeting SOS1 and ERK2, miR-20b inhibits the activity of the MAPK/ERK signaling pathway. The findings suggest that miR-20b may play an important role in PTC initiation, progression, and metastasis, and may provide a potential therapeutic target for PTC.

SpMYB overexpression in tobacco plants leads to altered abiotic and biotic stress responses.

The MYB transcription factors are involved in various plant biochemistry and physiology processes and play a central role in plant defense response. In the present study, a full-length cDNA sequence of a MYB gene, designated as SpMYB, was isolated from tomato. SpMYB encodes the R2R3-type protein consisting of 328 amino acids. The expression level of SpMYB was strongly induced by fungal pathogens. Transgenic tobacco plants overexpressing SpMYB had an enhanced salt and drought stress tolerance compared with wild-type plants, and showed significantly improved resistance to Alternaria alternate. Further analysis revealed that transgenic tobaccos exhibited less accumulation of malondialdehyde (MDA) and more accumulation of superoxide dismutase (SOD), peroxidase (POD) and phenylalanine ammonia-lyase (PAL) after inoculation with A. alternate. Meanwhile, changes in some photosynthetic parameters, such as photosynthetic rate (Pn), transpiration rate (Tr) and intercellular CO2 concentration (Ci) were also found in the transgenic tobaccos. Furthermore, transgenic tobaccos constitutively accumulated higher levels of pathogenesis-related (PR) gene transcripts, such as PR1 and PR2. The results suggested that the tomato SpMYB transcription factor plays an important role in responses to abiotic and biotic stress.