Assessing the Role of Gaseous Chlorine Dioxide in Modulating the Postharvest Ripening of Keitt Mangoes through the Induction of Ethylene Biosynthesis.

Consumer acceptance of Keitt mangoes (Mangifera indica L.) is significantly affected by their slow postharvest ripening. This work used gaseous chlorine dioxide (ClO2(g)) to prepare the ready-to-eat Keitt mango and explored the potential mechanisms for the mango ripening. Harvested mangoes were treated with 20 mg·L-1 of ClO2(g) or ethephon for 3 h (25 °C) and left in a climatic chamber with a temperature of 25 ± 1 °C and a relative humidity of 85 ± 5% for 4 d. The results showed that ClO2(g) treatment significantly promoted the orange coloration of mango flesh compared to the untreated control group. Moreover, ClO2(g) treatment significantly elevated the total soluble solids, total soluble sugar, and total carotenoids content of mangoes, whereas the firmness and titratable acidity were reduced. ClO2(g)-treated mangoes reached the edible window on day 2, as did mangoes treated with ethephon at the same concentration, except that the sweetness was prominent. The residual ClO2 level of the mangoes was <0.3 mg/kg during the whole storage time, which is a safe level for fruit. In addition, ClO2(g) significantly advanced the onset of ethylene peaks by 0.5 days and increased its production between days 0.5 and 2 compared to the control group. Consistently, the genes involved in ethylene biosynthesis including miACS6, miACO1, and miACO were upregulated. In sum, ClO2(g) can be a potential technique to reduce the time for harvested mango to reach the edible window, and it functions in modulating postharvest ripening by inducing ethylene biosynthesis.

Risk of adverse pregnancy outcomes in pregnant women with gestational diabetes mellitus by age: a multicentric cohort study in Hebei, China.

Gestational diabetes mellitus (GDM) is an unique metabolic disorder that occurs during pregnancy. Both GDM and advanced age increase the risk of adverse pregnancy outcomes. This study used a GDM cohort study to investigate the role of age in the adverse pregnancy outcomes for pregnant women with GDM. From 2015 to 2021, 308,175 pregnant women were selected, and the data received from 22 hospitals by the Hebei Province Maternal Near Miss Surveillance System. There were 24,551 pregnant women with GDM that were divided into five groups by age (20-24, 25-29, 30-34, 35-39, 40-44 years old). Because the prevalence of adverse pregnancy outcomes was lower in pregnant women with GDM aged 25-29, they were used as a reference group (P < 0.05). Compared with GDM women aged 25-29 years, GDM women aged 35-44 years had a significant higher risk of cesarean delivery (aOR: 2.86, 95% CI 2.52-3.25) (P < 0.001), abnormal fetal position (aOR: 1.78, 95% CI 1.31-2.37) (P < 0.001), pre-eclampsia (aOR: 1.28, 95% CI 1.01-1.61) (P < 0.05), macrosomia (aOR: 1.25, 95% CI 1.08-1.45) (P < 0.05), and large for gestational age (LGA) (aOR: 1.16, 95% CI 1.02-1.31) (P < 0.05), GDM women aged 40-44 years had a higher risk of placenta previa (aOR: 2.53, 95% CI 1.01-6.35) (P < 0.05), anemia (aOR: 3.45, 95% CI 1.23-9.68) (P < 0.05) and small for gestational age (aOR: 1.32, 95% CI 1.01-1.60) (P < 0.05). Advanced maternal age was an independent risk factor for abnormal fetal position, pre-eclampsia, anemia, macrosomia, and LGA in pregnant women with GDM.

Prevalence and adverse perinatal outcomes of anaemia in the third trimester of pregnancy in Hebei Province, China.

BACKGROUND: Anaemia in pregnancy is one of the most frequent complications related to pregnancy and is a public health concern. This article examines the prevalence of anaemia in the third trimester of pregnancy and the associations between anaemia and adverse perinatal outcomes in Hebei Province, China. METHODS: We used SPSS software to describe the incidence of anaemia in the third trimester of pregnancy in Hebei Province and analysed the clinical characteristics in anaemic patients and the relationship between anaemia and adverse pregnancy outcomes. RESULTS: The overall prevalence of anaemia in the third trimester of pregnancy was 35.0% in Hebei Province. The prevalence of anaemia in the population with a high education level was lower than that in the population with a low education level. The incidence rate in rural areas was higher than that in urban areas. After adjustment for confounding factors, anaemia in the third trimester of pregnancy is an independent risk factor in terms of placenta previa, placental abruption, uterine atony, pre-eclampsia, gestational diabetes mellitus, heart disease, postpartum haemorrhage, premature birth, laceration of birth canal, puerperal infection, caesarean section and large for gestational age. CONCLUSIONS: The prevalence of anaemia in the third trimester of pregnancy is associated with an increased risk of adverse perinatal outcomes. A comprehensive approach to prevent anaemia is needed to improve maternal and child health outcomes.

miR-6076 targets BCL6 in SH-SY5Y cells to regulate amyloid-ß-induced neuronal damage.

Amyloid-ß1-42 (Aß1-42 ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-ß (Aß)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aß1-42 . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aß1-42 -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aß1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aß1-42 -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aß-induced neuronal damage in AD.

Lama2 And Samsn1 Mediate the Effects of Brn4 on Hippocampal Neural Stem Cell Proliferation and Differentiation.

The transcription factor Brn4 exhibits vital roles in the embryonic development of the neural tube, inner ear, pancreas islet, and neural stem cell differentiation. Our previous studies have shown that Brn4 promotes neuronal differentiation of hippocampal neural stem cells (NSCs). However, its mechanism is still unclear. Here, starting from the overlapping genes between RNA-seq and ChIP-seq results, we explored the downstream target genes that mediate Brn4-induced hippocampal neurogenesis. There were 16 genes at the intersection of RNA-seq and ChIP-seq, among which the Lama2 and Samsn1 levels can be upregulated by Brn4, and the combination between their promoters and Brn4 was further determined using ChIP and dual luciferase reporter gene assays. EdU incorporation, cell cycle analysis, and CCK-8 assay indicated that Lama2 and Samsn1 mediated the inhibitory effect of Brn4 on the proliferation of hippocampal NSCs. Immunofluorescence staining, RT-qPCR, and Western blot suggested that Lama2 and Samsn1 mediated the promoting effect of Brn4 on the differentiation of hippocampal NSCs into neurons. In conclusion, our study demonstrates that Brn4 binds to the promoters of Lama2 and Samsn1, and they partially mediate the regulation of Brn4 on the proliferation inhibition and neuronal differentiation promotion of hippocampal NSCs.

The Effect of 2016 Chinese second-child policy and different maternal age on pregnancy outcomes in Hebei Province, China.

OBJECTIVE: To explore the effect of the 2016 Chinese second child policy and different maternal ages on adverse perinatal outcomes. METHODS: Clinical data were collected from 22 monitoring hospitals in Hebei Province from January 1, 2013, to December 31, 2021. A total of 413,892 parturient were divided into 3 groups based on delivery age: 20-34, 35-39, and 40-55 years old. The clinical data were analyzed to explore the relationship among the 2016 Chinese second-child policy, maternal age, and various pregnancy risks. RESULTS: Pregnancy complications showed an upward trend from 2013 to 2021.The top 10 incidences of pregnancy complications in Hebei Province were anemia, small for gestational age (SGA), large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM), premature delivery, preeclampsia (PE), postpartum hemorrhage (PPH), placenta previa, and placental abruption. The two-child policy was implemented in 2016. The incidence of pregnancy complications, anemia, GDM, PE, placental abruption, cesarean delivery, premature delivery, SGA, LGA, macrosomia in 2016-2021 was significantly higher than that in 2013-2015 (P<0.05), and the proportion of women of advanced maternal age (AMA, ≥ 35 years old) increased from 2013 to 2021. Advanced maternal age was a risk factor for most assessed adverse pregnancy outcomes, including GDM, PE, placenta previa, placenta abruption, cesarean delivery, PPH, premature delivery, SGA, LGA and macrosomia. CONCLUSION: After the adjustment of the "second-child" policy, the incidence of pregnancy complications increased. Moreover, the risk of adverse pregnancy outcomes in AMA has increased. Early prevention and intervention should be implemented to cope with the occurrence of adverse perinatal outcomes.

miR-6216 regulates neural stem cell proliferation by targeting RAB6B.

Neural stem cells (NSCs) are a class of self-renewing, multipotent and undifferentiated progenitor cells that retain the capacity to both glial and neuronal lineages. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in stem cell fate determination and self-renewal. Our previous RNA-seq data indicated that the expression of miR-6216 was decreased in denervated hippocampal exosomes compared with normal. However, whether miR-6216 participates in regulating NSC function remains to be elucidated. In this study, we demonstrated that miR-6216 negatively regulates RAB6B expression. Forced overexpression of miR-6216 inhibited NSC proliferation, and overexpression of RAB6B promoted NSC proliferation. These findings suggest that miR-6216 played an important role in regulating NSC proliferation via targeting RAB6B, and improve the understanding of the miRNA-mRNA regulatory network that affects NSC proliferation.

Application of interaction models in predicting the simultaneous growth of Staphylococcus aureus and different concentrations of background microbiota in Chinese-style braised beef.

This study aimed to investigate the growth kinetics of S. aureus and different concentrations of background microbiota in Chinese-style braised beef (CBB). A one-step analysis method was applied to develop predictive model to describe the simultaneous growth and interaction of S. aureus with different concentrations of background microbiota in CBB. The results show that a one-step method successfully models the growth of S. aureus and background microbiota in CBB and the competing interactions between the two. In sterile CBB, the estimated minimum growth temperatures (Tmin,S) and the maximum growth concentrations (Ymax,S) were 8.76 °C and 9.58 log CFU/g for S. aureus. Under competition, the growth of background microbiota was not affected by S. aureus, the estimated Tmin,B and Ymax,B was 4.46 °C and 9.94 log CFU/g. The background microbiota in CBB did not affect the growth rate of S. aureus (α1 = 1.04), but had an inhibitory effect on the number of S. aureus (α2 = 0.69) at the later growth stage. The Root Mean Square Error (RMSE) of the modeling data was 0.34 log CFU/g, with 85.5% of the residual errors within ±0.5 log CFU/g of experimental observations. The one-step analysis and dynamic temperatures (8 °C-32 °C) verification indicated that the RMSE of prediction was <0.5 log CFU/g for both S. aureus and background microbiota. This study demonstrates that microbial interaction models are a useful and promising tool for predicting and evaluating the spatiotemporal population dynamics of S. aureus and background microbiota in CBB products.

Secular increase in the prevalence of gestational diabetes and its associated adverse pregnancy outcomes from 2014 to 2021 in Hebei province, China.

Objective: We aimed to investigate the secular prevalence of gestational diabetes mellitus (GDM) and evaluate its adverse pregnancy outcomes among pregnant women in Hebei province, China. Methods: We analyzed the data from the monitoring information management system for pregnant women in 22 hospitals of Hebei province, China. In this study, 366,212 individuals with singleton live births from 2014 to 2021 were included, of whom 25,995 were diagnosed with gestational diabetes. We described the incidence of common complications and further analyzed the clinical characteristics in GDM patients and the relationship between GDM and adverse pregnancy outcomes. Results: The top 3 pregnancy complications in Hebei province are anemia, gestational hypertension, and GDM. The average incidence of GDM was 7.10% (25,995/366,212). The incidence rate of GDM significantly increased from 2014 to 2021 (χ2 trend = 7,140.663, P < 0.001). The top 3 regions with GDM incidence were Baoding (16.60%), Shijiazhuang (8.00%), and Tangshan (3.80%). The incidence of GDM in urban pregnant women (10.6%) is higher than that in rural areas (3.7%).The difference between the GDM and Non-GDM groups was statistically significant in terms of maternal age, gravidity, parity, education level, and incidence of pregnancy complications (gestational hypertension, heart diseases, and anemia) (P < 0.05). GDM individuals were at significantly increased risk of most assessed adverse pregnancy outcomes, including premature delivery, Cesarean delivery, uterine inertia, neonatal intensive care unit (NICU) admission, Apgar (activity-pulse-grimace-appearance-respiration) score at 1 min, and macrosomia (P < 0.05). The multivariate logistic regression analysis showed that GDM was an independent risk factor in terms of premature birth, Cesarean delivery, uterine inertia, placental abruption, NICU admission, and macrosomia. Conclusion: The risk of adverse pregnancy outcome in pregnant women with GDM is significantly increased. In order to reduce the occurrence of adverse pregnancy outcomes, effective interventions are needed.

Barley Leaf Ameliorates Citrobacter rodentium-Induced Colitis through Preventive Effects.

The incidence and prevalence of inflammatory bowel disease (IBD) have been increasing globally and progressively in recent decades. Barley leaf (BL) is a nutritional supplement that is shown to have health-promoting effects on intestinal homeostasis. Our previous study demonstrated that BL could significantly attenuate Citrobacter rodentium (CR)-induced colitis, but whether it exerts a prophylactic or therapeutic effect remains elusive. In this study, we supplemented BL before or during CR infestation to investigate which way BL acts. The results showed that BL supplementation prior to infection significantly reduced the disease activity index (DAI) score, weight loss, colon shortening, colonic wall swelling, and transmissible murine colonic hyperplasia. It significantly reduced the amount of CR in the feces and also markedly inhibited the extraintestinal transmission of CR. Meanwhile, it significantly reduced the levels and expression of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFNγ), and interleukin-1ß (IL1ß). In addition, pretreatment with BL improved CR-induced gut microbiota dysbiosis by reducing the content of Proteobacteria, while increasing the content of Lactobacillus. In contrast, the effect of BL supplementation during infestation on the improvement of CR-induced colitis was not as good as that of pretreatment with BL. In conclusion, BL protects against CR-caused colitis in a preventive manner.

Exogenous proline enhances susceptibility of NSCLC to cisplatin via metabolic reprogramming and PLK1-mediated cell cycle arrest.

The occurrence of cisplatin resistance is still the main factor limiting the therapeutic effect of non-small cell lung cancer (NSCLC). It is urgent to elucidate the resistance mechanism and develop novel treatment strategies. Targeted metabolomics was first performed to detect amino acids' content in cisplatin-resistant cancer cells considering the relationship between tumour metabolic rearrangement and chemotherapy resistance and chemotherapy resistance. We discovered that levels of most amino acids were significantly downregulated, whereas exogenous supplementation of proline could enhance the sensitivity of NSCLC cells to cisplatin, evidenced by inhibited cell viability and tumour growth in vitro and xenograft models. In addition, the combined treatment of proline and cisplatin suppressed ATP production through disruption of the TCA cycle and oxidative phosphorylation. Furthermore, transcriptomic analysis identified the cell cycle as the top enriched pathway in co-therapy cells, accompanied by significant down-regulation of PLK1, a serine/threonine-protein kinase. Mechanistic studies revealed that PLK1 inhibitor (BI2536) and CDDP have synergistic inhibitory effects on NSCLC cells, and cells transfected with lentivirus expressing shPLK1 showed significantly increased toxicity to cisplatin. Inhibition of PLK1 inactivated AMPK, a primary regulator of cellular energy homeostasis, ultimately leading to cell cycle arrest via FOXO3A-FOXM1 axis mediated transcriptional inhibition in cisplatin-resistant cells. In conclusion, our study demonstrates that exogenous proline exerts an adjuvant therapeutic effect on cisplatin resistance, and PLK1 may be considered an attractive target for the clinical treatment of cisplatin resistance in NSCLC.

Chemical features and biological functions of water-insoluble dietary fiber in plant-based foods.

Insoluble dietary fiber (IDF) is a nutritional component constituting the building block of plant cell walls. Our understanding of the role of IDF in plant-based foods has advanced dramatically in recent years. In this Review, we summarize research progress on the subtypes, structure, analysis, and extraction methods of IDF. The impact of different food processing methods on the properties of IDF is discussed. The role of gut microbiota in the health benefits of IDF is introduced. This review provides a better understanding of the chemical features and biological functions of IDF, which may promote the future application of IDF in functional food products. Further investigation of the mechanisms underlying the health benefits of IDF enables the development of effective strategies for the prevention and treatment of human diseases.

MiR-130a-3p regulates neural stem cell differentiation in vitro by targeting Acsl4.

In the adult mammalian brain, neural stem cells (NSCs) are the precursor cells of neurons that contribute to nervous system development, regeneration, and repair. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cell fate determination and differentiation by negatively regulating gene expression. Here, we identified a post-transcriptional mechanism, centred around miR-130a-3p that regulated NSC differentiation. Importantly, overexpressing miR-130a-3p promoted NSC differentiation into neurons, whereas inhibiting miR-130a-3p function reduced the number of neurons. Then, the quantitative PCR, Western blot and dual-luciferase reporter assays showed that miR-130a-3p negatively regulated acyl-CoA synthetase long-chain family member 4 (Acsl4) expression. Additionally, inhibition of Acsl4 promoted NSC differentiation into neurons, whereas silencing miR-130a-3p partially suppressed the neuronal differentiation induced by inhibiting Acsl4. Furthermore, overexpressing miR-130a-3p or inhibiting Acsl4 increased the levels of p-AKT, p-GSK-3ß and PI3K. In conclusion, our results suggested that miR-130a-3p targeted Acsl4 to promote neuronal differentiation of NSCs via regulating the Akt/PI3K pathway. These findings may help to develop strategies for stem cell-mediated treatment for central nervous system diseases.

circRNA Acbd6 promotes neural stem cell differentiation into cholinergic neurons via the miR-320-5p-Osbpl2 axis.

Neural stem cells (NSCs) persist in the dentate gyrus of the hippocampus into adulthood and are essential for both neurogenesis and neural circuit integration. Exosomes have also been shown to play vital roles in regulating biological processes of receptor cells as a medium for cell-to-cell communication signaling molecules. The precise molecular mechanisms of exosome-mediated signaling, however, remain largely unknown. Here, we found that exosomes produced by denervated hippocampi following fimbria-fornix transection could promote the differentiation of hippocampal neural precursor cells into cholinergic neurons in coculture with NSCs. Furthermore, we found that 14 circular RNAs (circRNAs) were upregulated in hippocampal exosomes after fimbria-fornix transection using high-throughput RNA-Seq technology. We further characterized the function and mechanism by which the upregulated circRNA Acbd6 (acyl-CoA-binding domain-containing 6) promoted the differentiation of NSCs into cholinergic neurons using RT-quantitative PCR, Western blot, ELISA, flow cytometry, immunohistochemistry, and immunofluorescence assay. By luciferase reporter assay, we demonstrated that circAcbd6 functioned as an endogenous miR-320-5p sponge to inhibit miR-320-5p activity, resulting in increased oxysterol-binding protein-related protein 2 expression with subsequent facilitation of NSC differentiation. Taken together, our results suggest that circAcbd6 promotes differentiation of NSCs into cholinergic neurons via miR-320-5p/oxysterol-binding protein-related protein 2 axis, which contribute important insights to our understanding of how circRNAs regulate neurogenesis.

miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation.

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3' untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, ß-catenin, phosphor-GSK-3ß, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/ß-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

MiR-674-5p Suppresses the Proliferation and Migration of Glioma Cells by Targeting Cul4b.

Glioma multiforme (GBM) is the most common malignant primary brain tumors. Despite the considerable advances in GBM treatment, it is still one of the most lethal forms of brain tumor. New clinical biomarkers and therapeutic targets are immediately required. MicroRNAs (miRNAs) are a class of small, evolutionarily conserved noncoding RNAs and have emerged as the key regulators of many cancers. Here in this study, we showed that miR-674-5p was probably an important regulator of glioma cell growth. After the transfection with miR-674-5p mimic or inhibitor, we found that the expression level of miR-674-5p was negatively related with cell proliferation and migration in C6 cells. Based on the prediction of the target genes of miR-674-5p on the website, we chose Cullin 4B (Cul4b), a gene upregulated in GBM, and proved that it was a target of miR-674-5p. In addition, we explored the role of miR-674-5p in glioma growth in vivo. Taken together, the present study indicated that miR-674-5p suppressed glioma cell proliferation and migration by targeting Cul4b.

Dietary Barley Leaf Mitigates Tumorigenesis in Experimental Colitis-Associated Colorectal Cancer.

Dietary barley (Hordeum vulgare L.) leaf (BL) is a popular functional food known to have potential health benefits; however, the effect of BL in colorectal cancer prevention has not been examined. Here, we examined the role of BL on the prevention of colorectal carcinogenesis and defined the mechanism involved. BL supplementation could protect against weight loss, mitigate tumor formation, and diminish histologic damage in mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). Moreover, BL suppressed colonic expression of inflammatory enzymes, while improving the mucosal barrier dysfunctions. The elevated levels of cell proliferation markers and the increased expression of genes involved in ß-catenin signaling were also reduced by BL. In addition, analyses of microbiota revealed that BL prevented AOM/DSS-induced gut microbiota dysbiosis by promoting the enrichment of Bifidobacterium. Overall, these data suggest that BL is a promising dietary agent for preventing colitis-associated colorectal cancer.

P4HA2 promotes cell proliferation and migration in glioblastoma.

Glioblastoma (GBM) is a primary malignant tumor characterized by high infiltration and angiogenesis in the brain parenchyma. Glioma stem cells (GSCs), a heterogeneous GBM cell type with the potential for self-renewal and differentiation to tumor cells, are responsible for the high malignancy of GBM. The purpose of the present study was to investigate the roles of significantly differentially expressed genes between GSCs and GBM cells in GBM progression. The gene profiles GSE74304 and GSE124145, containing 10 GSC samples and 12 GBM samples in total, were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes were identified with GEO2R tools and Venn software online. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed on the 41 upregulated and 142 downregulated differentially expressed genes in GSCs compared with in GBM cells via the DAVID website. Protein-protein interaction and module analyses in Cytoscape with the STRING database revealed 21 hub genes that were downregulated in GSCs compared with in GBM cells. Survival analysis conducted via the GEPIA2 website revealed that low expression levels of the hub genes prolyl 4-hydroxylase subunit α2 (P4HA2), TGF-ß induced, integrin subunit α3 and thrombospondin 1 were associated with significantly prolonged survival time in patients with GBM. Further experiments were performed focusing on P4HA2. Reverse transcription-quantitative PCR was used to detect P4HA2 gene expression. In agreement with the bioinformatics analysis, P4HA2 expression was higher in U87 cells than in GSCs. Cell Counting Kit-8, EdU incorporation, cell cycle analysis, wound healing and Transwell assays demonstrated that the cell proliferation and migration increased after P4HA2 overexpression and decreased after P4HA2-knockdown. In conclusion, the present study demonstrated that low P4HA2 expression in GSCs promoted GBM cell proliferation and migration, suggesting that P4HA2 may act as a switch in the transition from GSCs to GBM cells.

CircHECTD1 Regulates Cell Proliferation and Migration by the miR-320-5p/SLC2A1 Axis in Glioblastoma Multiform.

Glioblastoma multiform (GBM) is the most common and malignant primary brain cancer in adults, and thus, novel potential therapeutic targets for diagnosis and treatment are urgently needed. Circular RNAs (circRNAs) are a class of widespread and diverse endogenous RNAs that have been suggested as potential critical mediators during progression of various tumors. In this study, we investigated the involvement of circHECTD1 in GBM progression. CircHECTD1 Lentivirus, miR-320-5p mimic, and SLC2A1 Lentivirus were transduced into cancer cells independently or together. circHECTD1, miR-320-5p, and SLC2A1 level were detected by qRT-PCR. Western blot and qRT-PCR were applied to measure the expression of SLC2A1, CyclinD1, CDK2, and PCNA. Flow cytometry, EdU, colony formation, Transwell and wound-healing assays were conducted to assess cell proliferation and migration. Luciferase reporter assays were performed to determine the effect of miR-320-5p on circHECTD1 or SLC2A1. Xenograft experiments were implemented to evaluate tumor growth in vivo. CircHECTD1 expression led to the promotion of proliferation and migration of GBM cells. In addition, circHECTD1 acted as a ceRNA to interact with miR-320-5p, which targeted the solute carrier family 2 member 1 (SLC2A1). In vivo experiments also revealed that circHECTD1 promoted tumor growth. Collectively, our findings showed that the circHECTD1-miR-320-5p-SLC2A1 regulatory pathway promoted the progression of GBM, suggesting that circHECTD1 may be a therapeutic target for GBM.