ALDH1+ tumor stem cells promote the progression of malignant fibrous tissue sarcoma by inhibiting SYNPO2 through hsa-mir-206.

This research aims to explore the mechanism by which microRNAs may regulate the biological behavior of tumor cells in ALDH1+ fibrosarcoma. We identified differentially expressed miRNAs in ALDH + NMFH-1 cells, screened genes related to sarcoma metastasis in the TCGA database, and finally obtained key genes regulated by miRNAs that are involved in metastasis. The function and mechanism of these key genes were then validated at the cellular level. Using the ULCAN database, a significant correlation was found between hsa-mir-206 and mortality in sarcoma patients. WGCNA analysis identified 352 genes related to tumor metastasis. Through Venn diagrams, we obtained 15 metastasis-related genes regulated by hsa-mir-206. Survival analysis showed that SYNPO2 expression is significantly correlated with survival rate and is significantly underexpressed in multiple tumors. SYNPO2 showed a negative correlation with macrophages and a positive correlation with CD8+ T cells. After inhibiting the expression of hsa-mir-206 with siRNA plasmids, the mRNA expression of SYNPO2 was significantly upregulated. The results of CCK8 assay, scratch assay, and transwell assay showed that the proliferation and migration ability of NFMH-1 cells were promoted after SYNPO2 was inhibited. ALDH1+ tumor stem cells promote the proliferation and invasion of malignant fibrous histiocytoma cells by inhibiting SYNPO2 through hsa-mir-206.

A fully coupled multiphase model for infrared-convective drying of sweet potato.

BACKGROUND: Combined infrared (CIR) and convective drying is a promising technology in dehydrating heat-sensitive foods, such as fruits and vegetables. This novel thermal drying method, which involves the application of infrared energy and hot air during a drying process, can drastically enhance energy efficiency and improve overall product quality at the end of the process. Understanding the dynamics of what goes on inside the product during drying is important for further development, optimization, and upscaling of the drying method. In this study, a multiphase porous media model considering liquid water, gases, and solid matrix was developed for the CIR and hot-air drying (HAD) of sweet potato slices in order to capture the relevant physics and obtain an in-depth insight on the drying process. The model was simulated using Matlab with user-friendly graphical user interface for easy coupling and faster computational time. RESULTS: The gas pressure for CIR-HAD was higher centrally and decreased gradually towards the surface of the product. This implies that drying force is stronger at the product core than at the product surface. A phase change from liquid water to vapour occurs almost immediately after the start of the drying process for CIR-HAD. The evaporation rate, as expected, was observed to increase with increased drying time. Evaporation during CIR-HAD increased with increasing distance from the centreline of the sample surface. The simulation results of water and vapour flux revealed that moisture transport around the surfaces and sides of the sample is as a result of capillary diffusion, binary diffusion, and gas pressure in both the vertical and horizontal directions. The nonuniform dominant infrared heating caused the heterogeneous distribution of product temperature. These results suggest that CIR-HAD of food occurs in a non-uniform manner with high vapour and water concentration gradient between the product core and the surface. CONCLUSIONS: This study provides in-depth insight into the physics and phase changes of food during CIR-HAD. The multiphase model has the advantage that phase change and impact of CIR-HAD operating parameters can be swiftly quantified. Such a modelling approach is thereby significant for further development and process optimization of CIR-HAD towards industrial upscaling. © 2020 Society of Chemical Industry.

Systematic study of cis-antisense miRNAs in animal species reveals miR-3661 to target PPP2CA in human cells.

MicroRNAs (miRNAs) suppress targeting gene expression through blocking translation or triggering mRNA degradation and, in general, act in trans, through a partially complementary interaction with the 3' untranslated region (3' UTR) or coding regions of a target gene. Although it has been reported previously that some miRNAs suppress their target genes on the opposite strand with a fully complementary sequence (i.e., natural antisense miRNAs that act in cis), there is no report to systematically study such cis-antisense miRNAs in different animal species. Here we report that cis-antisense miRNAs do exist in different animal species: 48 in Caenorhabditis elegans, 17 in Drosophila, 36 in Mus musculus, and 52 in Homo sapiens using a systematical bioinformatics approach. We show that most of these cis-antisense miRNAs can efficiently reduce the expression levels of their target genes in human cells. We further investigate hsa-miR-3661, one of the predicted cis-antisense miRNAs, in detail and demonstrate that this miRNA directly targets the coding sequence of PPP2CA located on the opposite DNA strand and inhibits the PPP2CA expression. Taken together, these results indicate that cis-antisense miRNAs are conservative and functional in animal species including humans.

Differences in Characteristics and Clinical Outcomes Among Hispanic/Latino Men and Women Receiving HIV Medical Care - United States, 2013-2014.

The prevalence of diagnosed human immunodeficiency virus (HIV) infection among Hispanics/Latinos in the United States is approximately twice that of non-Hispanic whites (1). Barriers to, and experiences with, medical care have been found to vary by sex (2). Describing characteristics of Hispanics/Latinos in care by sex can help identify disparities and inform delivery of tailored services to this underserved population. Data from the 2013 and 2014 cycles of the Medical Monitoring Project (MMP) were analyzed to describe demographic, behavioral, and clinical characteristics among Hispanics/Latinos by sex. MMP is an annual cross-sectional, nationally representative surveillance system that, during 2013-2014, collected information about behaviors, medical care, and clinical outcomes among adults receiving outpatient HIV care. Hispanic/Latina women were significantly more likely than were men to live in poverty (78% versus 54%), report not speaking English well (38% versus 21%), and receive interpreter (27% versus 16%), transportation (35% versus 21%), and meal (44% versus 26%) services. There were no significant differences between Hispanic/Latino women and men in prescription of antiretroviral therapy (ART) (95% versus 96%) or sustained viral suppression (68% versus 73%). Although women faced greater socioeconomic and language-related challenges, the clinical outcomes among Hispanic/Latina women were similar to those among men, perhaps reflecting their higher use of ancillary services. Levels of viral suppression for Hispanics/Latinos are lower than those found among non-Hispanic whites (3) and lower than the national prevention goal of at least 80% of persons with diagnosed HIV infection. Providers should be cognizant of the challenges faced by Hispanics/Latinos with HIV infection in care and provide referrals to needed ancillary services.

The potential of computer vision, optical backscattering parameters and artificial neural network modelling in monitoring the shrinkage of sweet potato (Ipomoea batatas L.) during drying.

BACKGROUND: Drying is a method used to preserve agricultural crops. During the drying of products with high moisture content, structural changes in shape, volume, area, density and porosity occur. These changes could affect the final quality of dried product and also the effective design of drying equipment. Therefore, this study investigated a novel approach in monitoring and predicting the shrinkage of sweet potato during drying. Drying experiments were conducted at temperatures of 50-70 °C and samples thicknesses of 2-6 mm. The volume and surface area obtained from camera vision, and the perimeter and illuminated area from backscattered optical images were analysed and used to evaluate the shrinkage of sweet potato during drying. RESULTS: The relationship between dimensionless moisture content and shrinkage of sweet potato in terms of volume, surface area, perimeter and illuminated area was found to be linearly correlated. The results also demonstrated that the shrinkage of sweet potato based on computer vision and backscattered optical parameters is affected by the product thickness, drying temperature and drying time. A multilayer perceptron (MLP) artificial neural network with input layer containing three cells, two hidden layers (18 neurons), and five cells for output layer, was used to develop a model that can monitor, control and predict the shrinkage parameters and moisture content of sweet potato slices under different drying conditions. The developed ANN model satisfactorily predicted the shrinkage and dimensionless moisture content of sweet potato with correlation coefficient greater than 0.95. CONCLUSION: Combined computer vision, laser light backscattering imaging and artificial neural network can be used as a non-destructive, rapid and easily adaptable technique for in-line monitoring, predicting and controlling the shrinkage and moisture changes of food and agricultural crops during drying. © 2017 Society of Chemical Industry.

MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R.

BACKGROUND/AIMS: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. METHODS: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR). The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. RESULTS: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. CONCLUSION: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma.

Distinct roles of Ape1 protein, an enzyme involved in DNA repair, in high or low linear energy transfer ionizing radiation-induced cell killing.

High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (≤40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy.

BMI levels with MS Bone mineral density levels in adults with multiple sclerosis: a meta-analysis.

INTRODUCTION: Multiple sclerosis (MS) and osteoporosis (OP) affect a substantial proportion of the population. Accumulating evidence suggests that MS patients are at high risk for OP. We performed a meta-analysis to identify risk factors for lowered bone mineral density (BMD) in MS patients. METHODS: We searched for articles within the Medline, Embase and Cochrane Library databases, published up to March 2014, pertaining to associations between MS and BMD. A total of 11 studies was included in the meta-analysis. RESULTS: The analysis indicated that MS patients have reduced lumbar spine, femur neck, and hip BMD compared with healthy controls (lumbar spine, standardized mean difference (SMD) = -0.76, 95% CI: -1.07, -0.45; femur neck, SMD = -0.56, 95% CI: -0.84, -0.29; and hip, SMD = -0.62, 95% CI: -0.96, -0.29). Further subgroup analysis revealed that a disease duration of >7 years, total steroid dose during the disease of >15 g, and an Expanded Disability Status Scale (EDSS) score of > 3, increased the risk of reduced BMD in the lumbar spine and femoral neck, but not in the hip. Meta-regression analysis did not explain the heterogeneity in the clinical characteristics or outcome definitions. CONCLUSIONS: Our meta-analysis suggests that MS patients have reduced overall BMD compared with healthy controls. Furthermore, disease duration (>7 years), total steroid dose (>15 g), and EDSS score (>3) are risk factors for reduced BMD in MS patients.

Research and Technologies to Reduce Grain Postharvest Losses: A Review.

Reducing postharvest losses offers a significant opportunity to enhance food availability without requiring extra production resources. A substantial portion of cereal grain goes to waste annually due to a lack of science-based knowledge, unconscious handling practices, suboptimal technical efficiency, and inadequate infrastructure. This article extensively reviews losses occurring during postharvest operations across various crops, examining diverse postharvest operations in different countries. Recent advancements in postharvest technology research are thoroughly discussed. The primary obstacles and challenges hindering the adoption and implementation of postharvest technologies are also explored. The appropriate postharvest technology relies on specific factors, including the kind of crops, production locales, seasons, and existing environmental and socioeconomic conditions.

A Retrospective Study of 91 Patients Treated with Percutaneous Kyphoplasty for Mild Osteoporotic Vertebral Compression Fractures and a New Evaluation Scale of Shape and Filling Effect of Cement.

BACKGROUND: Percutaneous kyphoplasty (PKP) is commonly used to treat severe osteoporotic vertebral compression fractures (OVCFs) by restoring vertebral height. However, its application in mild cases is not frequently discussed. METHODS: The study retrospectively included 100 treated vertebral bodies of the 91 patients mentioned before, and efficacy was evaluated using visual analog scale (VAS) and Oswestry Disability Index (ODI) scores preoperatively, 2 days postoperatively, and at 1 and 6 months after treatment, as well as mean variation in vertebral body height. The study also examined complications such as pain recurrence, delayed vertebral fracture, and loss of vertebral height, and developed a scale to assess the shape and filling effect of cement (SFEC) and its impact on complications. RESULTS: The results showed significant reductions in mean VAS and ODI scores from pre-to post-surgery and an increase in vertebral body height. However, complications occurred in 10 patients who received treatment for 11 vertebral bodies, including pain recurrence, fractures, and loss of vertebral height. Among the 10 patients with complications, 7 (63.6%) vertebral bodies had dissatisfied SFEC scores, compared with 22 (24.7%) vertebral bodies with dissatisfied SFEC scores in 81 patients without complications (89 vertebral bodies). CONCLUSIONS: PKP is a safe and effective method for treating mild OVCFs, but attention should be paid to the shape and filling effects of cement during surgery to prevent later complications. The developed SFEC scale provides a specific and quantitative standards for evaluating the recovery status after PKP, which need further validations.

Micro- and nanoplastics in agricultural soils: Assessing impacts and navigating mitigation.

Micro-/nanoplastic contamination in agricultural soils raises concerns on agroecosystems and poses potential health risks. Some of agricultural soils have received significant amounts of micro-/nanoplastics (MNPs) through plastic mulch film and biosolid applications. However, a comprehensive understanding of the MNP impacts on soils and plants remains elusive. The interaction between soil particles and MNPs is an extremely complex issue due to the different properties and heterogeneity of soils and the diverse characteristics of MNPs. Moreover, MNPs are a class of relatively new anthropogenic pollutants that may negatively affect plants and food. Herein, we presented a comprehensive review of the impacts of MNPs on the properties of soil and the growth of plants. We also discussed different strategies for mitigating or eliminating MNP contamination. Moreover, perspectives for future research on MNP contamination in the agricultural soils are also highlighted.

Kinetic mechanism of wheat straw pellets combustion process with a thermogravimetric analyser.

In this study, the combustion characteristics of two wheat straw pellets (WSP) (T1: 100% wheat straw and T5: 70% wheat straw; 10% sawdust, 10% biochar; 10% bentonite clay) were performed at a heating rate 20 °C/min under a temperature from 25 to 1200 °C in air atmosphere. A thermogravimetric analyser (TGA) was used to investigate the activation energy (Eα), pre-exponential factor (A), and thermodynamic parameters. The DTG/TG profile of WSP was evaluated by model-free and model-based methods and found the model-based method was suitable for WSP thermal characterisation. The result demonstrates that the thermal decomposition occurred in four stages, comprising four consecutive reaction steps. A→B→C→D→E→F. Further, the model-based techniques were best fitted with kinetic reaction models like Cn (nth-order reaction with auto-catalyst), Fn (reaction of nth order), F2 (second-order phase interfacial reaction) and D3 (diffusion control). The average Eα for Fn, Cn, D3 and F2 models were 164.723, 189.782, 273.88, and 45.0 kJ/mol, respectively, for the T1 pellets. Alternatively, for T5 pellets, the A was 1.17E+2, 1.76E+16, 5.5E+23, and 1.1E+3 (1/s) for F2, D3, Cn and Fn models. Overall, the thermodynamic properties showed that WSP thermokinetic reactions were complex and multi-point equilibrium, indicating a potentiality as a bioenergy feedstock.

Exosome miR-4738-3p-mediated regulation of COL1A2 through the NF-κB and inflammation signaling pathway alleviates osteoarthritis low-grade inflammation symptoms.

This study aimed to elucidate the roles of microRNA (miR)-4738-3p and the collagen type I alpha 2 chain (COL1A2) gene in the pathogenesis of osteoarthritis (OA) through bioinformatics analysis and cellular assays. The GSE55235 dataset was analyzed using the weighted gene co-expression network analysis (WGCNA) method to identify gene modules associated with OA. Key overlapping genes were identified from these modules and the GSE55235-differential expressed genes (DEGs). The expression levels of selected genes were determined in C28/I2 cells using the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-4738-3p and COL1A2 was examined in the context of interleukin 1 beta (IL-1ß) induction. Exosome characterization was achieved through transmission electron microscopy (TEM), western blotting (WB), and other analyses. The study also investigated the functional relevance of miR-4738-3p in OA pathology through various molecular and cellular assays. Our findings revealed that the green module exhibited a strong correlation with the OA phenotype in the GSE55235 dataset, with COL1A2 emerging as a hub gene and miR-4738-3p as its key downstream target. IL-1ß induction suggested that COL1A2 is involved in inflammation and apoptosis, while miR-4738-3p appeared to play an antagonistic role. The analysis of exosomes underscored the significance of miR-4738-3p in cellular communication, with an enhanced level of exo-miR-4738-3p antagonizing IL-1ß-induced inflammation and promoting cell survival. Conversely, a reduction in exo-miR-4738-3p led to increased cell damage. This study established a clear regulatory relationship between miR-4738-3p and COL1A2, with the nuclear factor kappa B (NF-κB) signaling pathway playing a central role in this regulation. The miR-4738-3p significantly influences the OA-associated inflammation, primarily through modulation of COL1A2 and the NF-κB pathway. Therefore, targeting miR-4738-3p offers a potential therapeutic approach for OA, with exosome miR-4738-3p presenting a promising strategy.

Effects of High-Pressure Carbon Dioxide on the Sensory and Chemical Properties of Dried Dates and Its Toxicity against Galleria mellonella (L.) and Plodia interpunctella (Hübner).

ABSTRACT: The use of chemical pesticides can have many detrimental side effects, including environmental pollution, and be a threat to human health. Carbon dioxide (CO2) treatment, a relatively new method for storage pest management, can replace harmful chemicals. Dates, an important food worldwide, contains many minerals, fiber, and a variety of vitamins and are an important dried fruit export from Iran annually. Thus, control of the pests of dried dates by using eco-friendly agents that do not affect quality features are critical. In this study, larval mortality of the Indian meal moth (Plodia interpunctella (Hübner)) and the greater wax moth (Galleria mellonella (L.)), two key pests of stored products, especially dried dates, was studied after exposure to different CO2 pressures within 24 h. Mortality percentages of the third-instar larvae of both pests were increased with an increase in CO2 pressure. Sensory tests on the qualitative characteristics of the dates revealed that CO2 pressures did not affect their aroma, color, sweetness, sourness, crispness, firmness, and overall acceptance. The highest tested pressure (33.4 mol%) of CO2 also had no significant effects on the chemical properties of the date samples, including moisture content, pH, acidity, Brix value, reducing sugar, and total sugar. We conclude that atmospheric CO2 gas can provide a cost-effective and environmentally friendly method for controlling the insect pests of dried dates in addition to preserving their sensory and quality properties.

Expression Profile Analysis of Long Non-coding RNA in OVX Models-Derived BMSCs for Postmenopausal Osteoporosis by RNA Sequencing and Bioinformatics.

Osteoporosis (OP) has the characteristics of a systematically impaired bone mass, strength, and microstructure. Long non-coding RNAs (lncRNAs) are longer than 200 nt, and their functions in osteoporosis is yet not completely understood. We first harvested the bone marrow mesenchymal stem cells (BMSCs) from ovariectomy (OVX) and sham mice. Then, we systematically analyzed the differential expressions of lncRNAs and messenger RNAs (mRNAs) and constructed lncRNA-mRNA coexpression network in order to identify the function of lncRNA in osteoporosis. Totally, we screened 743 lncRNAs (461 upregulated lncRNAs and 282 downregulated lncRNAs) and 240 mRNAs (128 upregulated and 112 downregulated) with significantly differential expressions in OP compared to normal. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses to investigate the functions and pathways of the differential expression of messenger RNAs (mRNAs), a coexpressed network of lncRNA/mRNA. Quantitative PCR (qPCR) validated that the expressions of NONMMUT096150.1, NONMMUT083450.1, and NONMMUT029743.2 were all downregulated, whereas NONMMUT026970.2, NONMMUT051734.2, NONMMUT003617.2, and NONMMUT034049.2 were all upregulated in the OVX group. NONMMUT096150.1, as a key lncRNA in OP, was identified to modulate the adipogenesis of BMSCs. Further analysis suggested that NONMMUT096150.1 might modulate the adipogenesis of BMSCs via the peroxisome proliferator-activated receptor (PPAR) signaling pathway, AMPK signaling pathway, and the lipolysis regulation in adipocyte and adipocytokine signaling pathway. Our study expands the understanding of lncRNA in the pathogenesis of OP.

Repeatome-Based Phylogenetics in Pelargonium Section Ciconium (Sweet) Harvey.

The repetitive part of the genome (the repeatome) contains a wealth of often overlooked information that can be used to resolve phylogenetic relationships and test evolutionary hypotheses for clades of related plant species such as Pelargonium. We have generated genome skimming data for 18 accessions of Pelargonium section Ciconium and one outgroup. We analyzed repeat abundancy and repeat similarity in order to construct repeat profiles and then used these for phylogenetic analyses. We found that phylogenetic trees based on read similarity were largely congruent with previous work based on morphological and chloroplast sequence data. For example, results agreed in identifying a "Core Ciconium" group which evolved after the split with P. elongatum. We found that this group was characterized by a unique set of repeats, which confirmed currently accepted phylogenetic hypotheses. We also found four species groups within P. sect. Ciconium that reinforce previous plastome-based reconstructions. A second repeat expansion was identified in a subclade which contained species that are considered to have dispersed from Southern Africa into Eastern Africa and the Arabian Peninsula. We speculate that the Core Ciconium repeat set correlates with a possible WGD event leading to this branch.

An assessment of greenhouse gas emissions from the Australian vegetables industry.

Recently, partly due to the increasing carbon consciousness in the electorates and partly due to the imminent introduction of the Australian Government's Carbon Pollution Reduction Scheme (CPRS), estimating carbon footprints is becoming increasingly necessary in agriculture. By taking data from several sources, this study estimates the national greenhouse gas (GHG) emissions from a variety of farm inputs, for the 23 key vegetables crops grown in Australia. For the 121,122 ha of land occupied by vegetable farms, there are 1.1 MtCO(2)e GHG emissions or 9.2 tCO(2)e ha(-1). In total, 65% of total GHG emissions from the vegetable industry are due to electricity use for irrigation and post-harvest on-farm activities, 17% from soil N(2)O emissions due to N fertiliser use, 10% from agrochemicals, 7% through fossils fuels and 1% from on-farm machinery. The top four vegetables (by area), potatoes, lettuce, tomatoes and broccoli account for 29.1%, 7.9%, 5.9% and 7.2% of total GHG emissions from vegetables, respectively. However, the ratio of GHG emissions between the highest and lowest-emitting crops per hectare and per tonne, are different. Therefore, care must be exercised in carbon footprint labelling vegetable products to ensure that the labels reflect carbon emissions on a per tonnage basis.

Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression.

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

Hypoxia-induced let-7f-5p/TARBP2 feedback loop regulates osteosarcoma cell proliferation and invasion by inhibiting the Wnt signaling pathway.

Osteosarcoma (OS) is the most common bone tumor in children and adolescents and is characterized by high metastatic and recurrence rates. In the past, it has been shown that microRNAs may play critical roles in hypoxia-related OS proliferation and invasion. However, the mechanisms by which OS cells acquire this malignant phenotype have remained largely unknown. In the present study, we report that let-7f-5p and TARBP2 were expressed in lower amounts in human OS cell lines when compared with the hFOB normal human osteoblastic cell line; however, both types of cells were repressed by hypoxia. let-7f-5p and TARBP2 significantly inhibited the proliferation and invasion of OS cells. Furthermore, TARBP2 as a downstream and functional target of let-7f-5p regulated the expression of let-7f-5p, and there was a regulatory feedback loop between let-7f-5p and TARBP2. This loop reduced the expression of let-7f-5p and TARBP2 in OS cells to a very low level, which was induced by hypoxia. Furthermore, the hypoxia-induced let-7f-5p/TARBP2 feedback loop contributed to activation of the Wnt signaling pathway. Taken together, our data clearly showed that the feedback loop between let-7f-5p and TARBP2 induced by the hypoxia-promoted OS cell malignant phenotype increased with activation of the Wnt signaling pathway.