Prognostic factors in patients with thymoma who underwent surgery.

PURPOSE: Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients. MATERIALS AND METHODS: Patients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created. RESULTS: A total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma. CONCLUSION: Smoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.

Circular RNA CircPDS5B impairs angiogenesis following ischemic stroke through its interaction with hnRNPL to inactivate VEGF-A.

BACKGROUND: Ischemic stroke (IS) is the primary cause of mortality and disability worldwide. Circular RNAs (circRNAs) have been proposed as crucial regulators in IS. This study focused on the role of circPDS5B in IS and its underlying mechanism. METHOD: Transient middle cerebral artery occlusion (tMCAO) mice and glucose deprivation/reoxygenation (OGD/R)-exposed human brain microvascular endothelial cells (BMECs) were used as IS models. Expression levels of circPDS5B, heterogenous nuclear ribonucleoprotein L (hnRNPL), runt-related transcription factor-1 (Runx1), and Zinc finger protein 24 (ZNF24) were quantified by qRT-PCR. MTT, wound healing, transwell and tube formation assays were employed to evaluate the cell proliferation, migration, and angiogenesis, respectively. Moreover, RNA pull-down, and RIP assay were performed to investigate the interaction among circPDS5B, hnRNPL and vascular endothelial growth factor-A (VEGF-A). RESULTS: circPDS5B was significantly up-regulated in IS patients and tMCAO mice. Deficiency of circPDS5B relieved brain infarction and neuronal injury of tMCAO mice. OGD/R-induced apoptosis, inhibition in viability, migration, and angiogenesis in BMECs were dramatically abrogated by circPDS5B knockdown. Mechanistically, circPDS5B stabilized Runx1 and ZNF24 via recruiting hnRNPL, thereby suppressing the transcription and expression of VEGFA. hnRNPL silencing strengthened circPDS5B knockdown-mediated beneficial effect on IS. CONCLUSION: Altogether, our study showed that high expression of circPDS5B exacerbated IS through recruitment of hnRNPL to stabilize Runx1/ZNF24 and subsequently inactivate VEGFA. Our findings suggest circPDS5B may be a novel therapeutic target for IS.

Blueberry-Mulberry Extract Alleviates Cognitive Impairment, Regulates Gut Metabolites, and Inhibits Inflammation in Aged Mice.

Cognitive impairment is associated with aging; however, the underlying mechanism remains unclear. Our previous study found that polyphenol-rich blueberry-mulberry extract (BME) had an antioxidant capability and effectively alleviated cognitive impairment in a mouse model of Alzheimer's disease. Thus, we hypothesized that BME would improve cognitive performance in naturally aging mice and assessed its effects on related signaling pathways. Eighteen-month-old C57BL/6J mice were gavaged with 300 mg/kg/d of BME for 6 weeks. Behavioral phenotypes, cytokine levels, tight junction protein levels, and the histopathology of the brain were assessed, and 16S ribosomal RNA sequencing and targeted metabolome analyses were used for gut microbiota and metabolite measurements. Our results showed that the cognitive performance of aged mice in the Morris water maze test was improved after BME treatment, neuronal loss was reduced, IL-6 and TNF-α levels in the brain and intestine were decreased, and the levels of intestinal tight junction proteins (ZO-1 and occludin) were increased. Further, 16S sequencing showed that BME significantly increased the relative abundance of Lactobacillus, Streptococcus, and Lactococcus and decreased the relative abundance of Blautia, Lachnoclostridium, and Roseburia in the gut. A targeted metabolomic analysis showed that BME significantly increased the levels of 21 metabolites, including α-linolenic acid, vanillic acid, and N-acetylserotonin. In conclusion, BME alters the gut microbiota and regulates gut metabolites in aged mice, which may contribute to the alleviation of cognitive impairment and to inflammation inhibition in both the brain and the gut. Our results provide a basis for future research on natural antioxidant intervention as a treatment strategy for aging-related cognitive impairment.

The Prognosis of Pineal Parenchymal Tumors: Development and Validation of a Nomogram Based on Surveillance, Epidemiology and End Results.

BACKGROUND: Pineal parenchymal tumors are exceedingly rare, and optimal disease management has yet to be defined. In this study, we aimed to identify prognostic factors and establish a predictive model for the prognosis of patients with pineal parenchymal tumors. METHODS: All patients with pineal parenchymal tumors in the Surveillance, Epidemiology and End Results database between 1975 and 2019 were reviewed. Data were summarized, and survival was modeled with Cox regression analyses. In addition, a nomogram predicting 5- and 10-year survival probability for pineal parenchymal tumors was developed and validated. RESULTS: We found 691 pineal parenchymal and 1961 pineal region neoplasms during 1975 and 2019 resulting in an incidence of 35%. In total, 441 patients were excluded due to incomplete data. The final cohort was subdivided into groups based on tumor histology: pineocytomas, pineoblastomas, and pineal parenchymal tumors of intermediate differentiation. Multivariate Cox analysis identified age and beam radiation as prognostic factors in pineoblastomas. Age, histology, tumor size, extent of resection, radiation, and chemotherapy were selected to build a clinical nomogram. The C-index for the nomogram was 0.795 (95% confidence interval 0.738-0.852). The calibration curves of the 5- and 10-year survival rates showed good agreement between the nomogram predictions and actual observations. CONCLUSIONS: This nomogram is a convenient and precise tool for clinicians to evaluate prognosis of pineal parenchymal tumors.

Subclinical hemorrhagic nonfunctionning pituitary adenoma: pituitary gland function status, endoscopic endonasal transsphenoidal surgery, and outcomes.

OBJECTIVE: How do subclinical hemorrhages into nonfunctioning pituitary adenomas (NFPAs) influence the hormonal status and surgical outcomes remains unclear, our study aim at evaluating its definite effects on pituitary gland function and surgical outcomes. METHODS: All 103 consecutive patients who underwent initial endoscopic endonasal approach (EEA) for NFPAs resection from June 2016 to June 2018 were retrospectively reviewed, depending on magnetic resonance imaging (MRI), operative and pathological findings, patients were divided into the non-hemorrhagic NFPAs group and the subclinical hemorrhagic NFPAs group. A comparative analysis was conducted between these two groups to investigate the effects of subclinical hemorrhages in NFPAs on pituitary endocrine function and surgical outcomes. RESULTS: The incidence of subclinical hemorrhage on NFPAs was 22.3% (23/103), which was more frequently observed in larger adenomas (28.9 ± 9.6 mm vs 19.2 ± 9.2 mm, p = 0.001). The incidence of preoperative hypopituitarism was 69.6% (16/23) for subclinical hemorrhagic NFPAs group and 31% (25/80) for non-hemorrhagic NFPAs group (p = 0.001), a high incidence of hypopituitarism for subclinical hemorrhagic NFPAs finally was found to be owing to the large tumor rather than the intratumoral hemorrhage. All those NFPAs were resected via EEA with the technology of extra-pseduocapusual dissection in a standard elective fashion. Postoperatively, there were more than 75.6% of patients with preoperative hypopituitarism had at least one axis recovered, with hyperprolactinemia resolved in 91.7% of patients, 94.7% headaches and 90% visual symptoms resolved or improved after surgery, there was no significant difference between these two groups (p > 0.05), indicates there was no any surgical outcome difference between NFPAs with or without subclinical hemorrhage. A very low postoperative complication was achieved with new postoperative anterior pituitary failure occurred in 9.7% of patients and permanent diabetes insipidus (DI) occurred in 9.7% of patients, which advocated that EEA can be chosen as a safe surgical treatment for subclinical hemorrhagic NFPAs. Furthermore, with the technology of extra-pseduocapusual dissection, more than 87% subclinical hemorrhagic NFPAs had achieved gross total resection (GTR) with a low incidence of new postoperative hypopituitarism (14%). CONCLUSION: Subclinical hemorrhage in NFPAs does not aggravate pituitary gland function. A surgical management strategy by EEA with the technology of extra-pseduocapusual dissection for the subclinical hemorrhagic NFPAs usually yields satisfactory endocrine and surgical outcomes, but it does not necessitate emergent tumor decompression.

Molecular diagnosis and treatment of meningiomas: an expert consensus (2022).

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION: Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.

Incision pressing, a simple and effective intervention to reduce colorectal surgical site infection: A propensity score-matched study.

Background: Colorectal surgery is associated with a high risk of surgical site infection (SSI). In March 2017, we developed an intervention, called "PRESS", with the aim of reducing colorectal superficial SSI. This study assessed the effect of the new intervention in reducing the rates of superficial SSI in colorectal surgery. Methods: This study was a retrospective review of 312 PRESS+ patients compared to 171 historical control PRESS- patients who were 18 years of age or older and underwent elective colorectal surgery with clean-contaminated wounds from January 2015 to June 2020. In the PRESS+ groups, we pressed the incision downward hard with clean gauze after the interrupted suturing of the skin. Propensity score matching with 15 variables was performed in a 1:1 ratio to reduce selection bias. Univariate analysis and multivariate analysis were performed to identify risk factors associated with SSI. Results: The characteristics of the PRESS+ (n = 160) and PRESS- (n = 160) groups were well balanced after propensity score matching. The PRESS+ group had a lower superficial SSI rate (1.9% vs. 6.9%, P = 0.029) and a lower overall SSI rate (2.5% vs. 10.0%, P = 0.006) than the PRESS- group. Furthermore, multivariate analysis showed that the incisional press was an effective protective factor for superficial SSI (adjusted odds ratio = 0.215, 95% confidence interval = 0.057-0.818, P = 0.024). In addition, female sex (P = 0.048) and blood transfusion (P = 0.011) were demonstrated to be independent risk factors for superficial SSI. Conclusion: The incisional press after suturing is a simple, costless, and effective intervention in reducing superficial incisional SSI.

Effects of early-life zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns.

OBJECTIVE: To investigate the effect of maternal zinc deficiency on learning and memory in offspring and the changes in DNA methylation patterns. METHODS: Pregnant rats were divided into zinc adequate (ZA), zinc deficient (ZD), and paired fed (PF) groups. Serum zinc contents and AKP activity in mother rats and offspring at P21 (end of lactation) and P60 (weaned, adult) were detected. Cognitive ability of offspring at P21 and P60 were determined by Morris water maze. The expression of proteins including DNMT3a, DNMT1, GADD45ß, MeCP2 and BDNF in the offspring hippocampus were detected by Western-blot. The methylation status of BDNF promoter region in hippocampus of offspring rats was detected by MS-qPCR. RESULTS: Compared with the ZA and PF groups, pups in the ZD group had lower zinc levels and AKP activity in the serum, spent more time finding the platform and spent less time going through the platform area. Protein expression of DNMT1 and GADD45b were downregulated in the ZD group during P0 and P21 but not P60 compared with the ZA and PF group, these results were consistent with a reduction in BDNF protein at P0 (neonate), P21. However, when pups of rats in the ZD group were supplemented with zinc ion from P21 to P60, MeCP2 and GADD45b expression were significantly downregulated compared with the ZA and PF group. CONCLUSION: Post-weaning zinc supplementation may improve cognitive impairment induced by early life zinc deficiency, whereas it may not completely reverse the abnormal expression of particular genes that are involved in DNA methylation, binding to methylated DNA and neurogenesis.

LncRNA RBPMS-AS1 promotes NRGN transcription to enhance the radiosensitivity of glioblastoma through the microRNA-301a-3p/CAMTA1 axis.

OBJECTIVE: Glioblastoma (GBM) is the most frequent brain malignancy with high incidence, and long noncoding RNAs (lncRNAs) exerts functions in GBM. In this research, we focused on the capabilities of lncRNA RBPMS-AS1 in radiosensitivity of GBM. METHODS: RBPMS-AS1 and CAMTA1 expression levels were determined in GBM tissues and cells. StarBase v3.0 database was searched for predicting miRNAs that simultaneously bound to RBPMS-AS1 and CAMTA1. pcDNA3.1-RBPMS-AS1, pcDNA3.1-CAMTA1, miR-301a-3p mimic, or pcDNA3.1-RBPMS-AS1/pcDNA3.1-CAMTA1 and miR-301a-3p mimic were transfected into GBM cells to test radiosensitivity, cell proliferation and apoptosis. The interactions of miR-301a-3p with RBPMS-AS1 and CAMTA1, as well as CAMTA1 and NRGN, were confirmed. In vivo imaging technology was utilized to detect tumor growth in orthotopic xenograft tumors, and Ki67 expression was tested in intracranial tumors. RESULTS: RBPMS-AS1 and CAMTA1 levels were reduced in GBM tissues and cells. miR-301a-3p had a binding site with both RBPMS-AS1 and CAMTA1 and it was the most significantly-upregulated one. Upregulation of RBPMS-AS1 or CAMTA1 enhanced the radiosensitivity and cell apoptosis while suppressing proliferation of GBM cells. Conversely, miR-301a-3p overexpression diminished the radiosensitivity and cell apoptosis while inducing proliferation of GBM cells. Overexpression of RBPMS-AS1 or CAMTA1 reversed the effects of overexpressed miR-301a-3p in GBM cells. Mechanistically, RBPMS-AS1 enhanced CAMTA1 expression in GBM cells through sponging miR-301a-3p, and CAMTA1 promoted NRGN expression. In animal experiments, overexpressed RBPMS-AS1 inhibited tumor growth and the positive expression of Ki67 both before and after radiation therapy. CONCLUSION: RBPMS-AS1 promotes NRGN transcription through the miR-301a-3p/CAMTA1 axis and enhances the radiosensitivity of GBM.

Association between circular stapler size and anastomotic leakage after laparoscopic low anterior resection for rectal cancer.

Background: Anastomotic leakage (AL) is one of the most severe and frequent complications occurring after laparoscopic low anterior resection (LAR) for rectal cancer. This study aimed to examine the association between circular stapler size and AL after laparoscopic LAR. Methods: This retrospective single-institution study involved 181 patients with rectal cancer who underwent laparoscopic LAR performed by a single surgical team between July 2016 and June 2021. The characteristics of the patients were analyzed. Risk factors for AL were identified via univariate and multivariate analyses. Additionally, a further propensity score matching (PSM) analysis was performed to reduce the selection bias. Results: Among the 181 patients who underwent laparoscopic LAR for rectal cancer, 17 (9.4%) developed clinical AL. In the univariate and multivariate analyses, male sex, incomplete intestinal obstruction, and the usage of a 32-mm stapler during the surgery were independent risk factors for the occurrence of AL. Furthermore, the PSM analysis confirmed that the incidence of AL with a 32-mm stapler was higher than that with a 29-mm stapler after laparoscopic low anterior resection. However, there was no difference in the incidence of anastomotic bleeding and stenosis. Conclusion: Choosing a smaller-diameter circular stapler may reduce the incidence of AL after laparoscopic LARfor rectal cancer without increasing the incidence of anastomotic stenosis.

Risk factors impacting intra- and postoperative cerebrospinal fluid rhinorrhea on the endoscopic treatment of pituitary adenomas: A retrospective study of 250 patients.

ABSTRACT: We aimed to identify the risk factors associated with intra- and postoperative cerebrospinal fluid (CSF) leakage in pituitary adenomas treated with endoscopic transsphenoidal surgery.This study is a retrospective analysis of 250 pituitary adenoma cases from January 2017 to December 2019 at our hospital. All patients underwent endoscopic endonasal transsphenoidal surgeries. Univariate and multivariate analyses were performed to investigate the risk factors associated with intra- and postoperative CSF rhinorrhea.Eighty (32.0%) and nine (3.6%) patients had intra- and postoperative CSF leakage, respectively. Tumor size was an independent risk factor for intraoperative CSF leakage (odds ratio [OR], 1.229; 95% confidence interval [CI], 1.133-1.334; P < .001); intraoperative CSF leakage was an independent risk factor for postoperative CSF leakage (OR, 7.707; 95% CI, 1.336-44.455; P = .022). Chronic respiratory disease (OR, 57.500; 95% CI, 8.031-411.682; P < .001) was also an independent risk factor for postoperative CSF leakage. Vascularized septal mucosal flap was a protective factor (OR, 0.107; 95% CI, 0.013-0.894; P = .039).Intraoperative CSF leakage is more likely to occur in large pituitary adenomas. In the presence of intraoperative CSF leakage, postoperative CSF rhinorrhea is very likely to occur. Patients with chronic respiratory disease are also more likely to develop postoperative CSF leakage. The sellar base reconstructed using vascularized nasal septal flaps can significantly decrease the risk. The Knosp grade, degree of tumor resection, and postoperative use of a lumbar subarachnoid drain did not have any effects on postoperative CSF rhinorrhea.

CD73-positive extracellular vesicles promote glioblastoma immunosuppression by inhibiting T-cell clonal expansion.

Extracellular vesicles are involved in the occurrence, progression and metastasis of glioblastoma (GBM). GBM can secrete a variety of tumour-derived extracellular vesicles (TDEVs) with high immunosuppressive activity that remotely suppress the systemic immune system, and therapy targeting TDEVs has potential efficacy. In this study, we detected a higher concentration of CD73+ TDEVs enriched in exosomes in central and peripheral body fluids of GBM patients than in those of patients with other brain tumours (low-grade glioma or brain metastases from melanoma or non-small-cell lung cancer). High CD73 expression was detected on the surface of T cells, and this CD73 was derived from TDEVs secreted by GBM cells. In vitro, we observed that CD73+ TDEVs released by GBM cell lines could be taken up by T cells. Moreover, excess adenosine was produced by AMP degradation around T cells and by adenosine receptor 2A (A2AR)-dependent inhibition of aerobic glycolysis and energy-related metabolic substrate production, thereby inhibiting the cell cycle entry and clonal proliferation of T cells. In vivo, defects in exosomal synthesis and CD73 expression significantly inhibited tumour growth in GBM tumour-bearing mice and restored the clonal proliferation of T cells in the central and peripheral regions. These data indicate that CD73+ TDEVs can be used as a potential target for GBM immunotherapy.

Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas.

Background: as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. Methods: the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. Results: GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. Conclusions: these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG.

SHANK2-FGFR1: A Novel FGFR1 Rearrangement in a Patient with Intestinal Adenocarcinoma.

Null.

Regulation of gliomagenesis and stemness through acid sensor ASIC1a.

Glioblastoma multiforme (GBM) is the most prevalent and aggressive type of adult gliomas. Despite intensive therapy including surgery, radiation, and chemotherapy, invariable tumor recurrence occurs, which suggests that glioblastoma stem cells (GSCs) render these tumors persistent. Recently, the induction of GSC differentiation has emerged as an alternative method to treat GBM, and most of the current studies aim to convert GSCs to neurons by a combination of transcriptional factors. As the tumor microenvironment is typically acidic due to increased glycolysis and consequently leads to an increased production of lactic acid in tumor cells, in the present study, the role of acid­sensing ion channel 1a (ASIC1a), an acid sensor, was explored as a tumor suppressor in gliomagenesis and stemness. The bioinformatics data from The Cancer Genome Atlas revealed that ASIC1 expression levels in GBM tumor tissues were lower than those in normal brain, and glioma patients with high ASIC1 expression had longer survival than those with low ASIC1 expression. Our immunohistochemistry data from tissue microarray revealed that ASIC1a expression was negatively associated with glioma grading. Functional studies revealed that the downregulation of ASIC1a promoted glioma cell proliferation and invasion, while upregulation of ASIC1a inhibited their proliferation and invasion. Furthermore, ASIC1a suppressed growth and proliferation of glioma cells through G1/S arrest and apoptosis induction. Mechanistically, ASIC1a negatively modulated glioma stemness via inhibition of the Notch signaling pathway and GSC markers CD133 and aldehyde dehydrogenase 1. ASIC1a is a tumor suppressor in gliomagenesis and stemness and may serve as a promising prognostic biomarker and target for GBM patients.

Differential Expression Profile of lncRNA in Glioma Cells and the Effect of lncRNA NKX3-1 on Glioma Cells Through Fem1b/SPDEF Pathway.

OBJECTIVE: To investigate the differential expression of lncRNA in glioma cells, as well as the effect of lncRNA NKX3-1 on glioma cells. METHODS: Glioma-related data were first downloaded from the TCGA database and analyzed using bioinformatics, after which the lncRNA NKX3-1 was chosen for further experiments. The expression of the lncRNA NKX3-1 in glioma tumor samples was detected using qRT-PCR. The subcellular localization of lncRNA NKX3-1 was determined using fluorescence in situ hybridization (FISH). CCK-8, flow cytometry, cell scratch, and transwell assays were used to detect cell proliferation, apoptosis, and invasion. The downstream pathway of lncRNA NKX3-1 was investigated using luciferase assays and detected using western blot, transwell, and cell scratch assays. RESULTS: The differential expression profile of lncRNA in glioma was obtained. NKX3-1 lncRNA was found to be significantly increased in glioma tumor tissues. LncRNA NKX3-1 was found in the nucleus. Proliferation, invasion, and migration of glioma cells were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group, while apoptosis ability was significantly decreased (P <0.05). Tumor volume and weight were significantly increased in the lncRNA NKX3-1 overexpression group in nude mice (P <0.05). LncRNA NKX3-1 significantly increased the luciferase activity of Fem1b 3'-UTR-WT reporter genes (P <0.05) as well as the levels of SPDEF protein (P <0.05). The protein level of FEM1B was significantly reduced. Cell invasion and migration were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group plus SPDEF group. CONCLUSION: We investigated the differential expression profile of lncRNAs in glioma and discovered that the lncRNA NKX3-1 plays an important role in cancer promotion via the Fem1b/SPDEF pathway.

Comprehensive Bioinformatics Analysis of mRNA Expression Profiles and Identification of a miRNA-mRNA Network Associated with the Pathogenesis of Low-Grade Gliomas.

PURPOSE: Low-grade glioma is the most common type of primary intracranial tumour, and the overall survival of patients with low-grade glioma (LGG) has shown no significant improvement over the past few decades. Therefore, it is crucial to understand the precise molecular mechanisms involved in the carcinogenesis of LGG. METHODS: To investigate the regulatory mechanisms of mRNA-miRNA networks related to LGG, in the present study, a comprehensive analysis of the genomic landscape between low-grade gliomas and normal brain tissues from the GEO and TCGA datasets was first conducted to identify differentially expressed genes (DEGs) and differentially expressed miRNAs in LGG. Following a series of analyses, including WGCNA, GO and KEGG analyses, PPI and key model analyses, and survival analysis of the DEGs with clinical phenotypes, the potential key genes were screened and identified, and the related miRNA-mRNA networks were subsequently constructed through miRWalk 3.0. Finally, the potential miRNA-mRNA networks were further validated in CGGA (Chinese Glioma Genome Atlas) datasets and clinical specimens by qRT-PCR. RESULTS: In our results, six hub genes, MELK, NCAPG, KIF4A, NUSAP1, CEP55, and TOP2A, were ultimately identified. Two regulatory pathways, miR-495-3p-TOP2A and miR-1224-3p-MELK, that regulate the pathogenesis of LGG were ultimately identified. Furthermore, the expression of miR-495-3p-TOP2A and miR-1224-3p-MELK in solid tissues was validated by qRT-PCR. CONCLUSION: Our study identified hub genes and related miRNA-mRNA regulatory pathways that contribute to the carcinogenesis of LGG, which may help us reveal the mechanisms underlying the development of LGG.

Prognostic significance of miR-203 and ZEB1 expression in early-stage hepatocellular carcinoma.

Background: Approximately one-quarter of patients with early-stage hepatocellular carcinoma (HCC) suffer from tumor recurrence within the first year after hepatectomy. Identification of patients at high risk of recurrence and new therapeutic approaches are crucial to improve clinical outcome. This study aimed to assess the prognostic significance of miR-203 and Zinc finger E-box binding homeobox 1 (ZEB1) in early-stage HCC and explore the association between the expression of ZEB1 and miR-203 in HCC. Methods: Tissue microarray-based immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to investigate ZEB1 and miR-203 expression in 73 patients with early-stage HCC and their correlation with clinicopathological features and prognosis of patients were analyzed. The prognostic value of the two factors was also measured by public KM plotter database. Quantitative reverse transcription PCR (qRT-PCR) assays were conducted to study the relationship between miR-203 and ZEB1. Transwell assays, Cell Counting Kit-8 (CCK-8) assays were performed to detect the roles of miR-203 in migration, invasion and proliferation of HCC cells. Results: We found low expression of miR-203 was associated significantly with tumor recurrence (P<0.001) and poor survival (P=0.020) of patients with early-stage HCC. Multivariate analysis revealed that low miR-203 expression was a poor prognostic factor for both overall survival (OS) (P=0.036) and recurrence free survival (RFS) (P=0.017). ZEB1 did not show any prognostic significance in our cohort. Correlation analysis indicated that there was no significant correlation between miR-203 and ZEB1 on both mRNA and protein levels. Furthermore, functional studies indicated that miR-203 repressed migration, invasion and proliferation of HCC cells in vitro. Conclusion: Our study suggested that miR-203 could be a novel predictor in early-stage HCC and might also be a potential molecular target for HCC therapy.

Transcriptional factor FoxM1-activated microRNA-335-3p maintains the self-renewal of neural stem cells by inhibiting p53 signaling pathway via Fmr1.

BACKGROUND: New mechanistic insights into the self-renewal ability and multipotent properties of neural stem cells (NSCs) are currently under active investigation for potential use in the treatment of neurological diseases. In this study, NSCs were isolated from the forebrain of fetal rats and cultured to induce NSC differentiation, which was associated with low expression of the non-coding RNA microRNA-335-3p (miR-335-3p). METHODS: Loss- and gain-of-function experiments were performed in NSCs after induction of differentiation. RESULTS: Overexpression of miR-335-3p or FoxM1 and inhibition of the Fmr1 or p53 signaling pathways facilitated neurosphere formation, enhanced proliferation and cell cycle entry of NSCs, but restricted NSC differentiation. Mechanistically, FoxM1 positively regulated miR-335-3p by binding to its promoter region, while miR-335-3p targeted and negatively regulated Fmr1. Additionally, the promotive effect of miR-335-3p on NSC self-renewal occurred via p53 signaling pathway inactivation. CONCLUSION: Taken together, miR-335-3p activated by FoxM1 could suppress NSC differentiation and promote NSC self-renewal by inactivating the p53 signaling pathway via Fmr1.

LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression.

In vitro and in vivo models of Parkinson's disease were established to investigate the effects of the lncRNA XIST/miR-199a-3p/Sp1/LRRK2 axis. The binding between XIST and miR-199a-3p as well as miR-199a-3p and Sp1 were examined by luciferase reporter assay and confirmed by RNA immunoprecipitation analysis. Following the Parkinson's disease animal behavioural assessment by suspension and swim tests, the brain tissue injuries were evaluated by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labelling, and tyrosine hydroxylase stainings. The results indicated that miR-199a-3p expression was downregulated, whereas that of XIST, Sp1 and LRRK2 were upregulated in Parkinson's disease. Moreover, miR-199a-3p overexpression or XIST knockdown inhibited the cell apoptosis induced by MPP+ treatment and promoted cell proliferation. The neurodegenerative defects were significantly recovered by treating the cells with shXIST or shSp1, whereas miR-199a-3p inhibition or Sp1 and LRRK2 overexpression abrogated these beneficial effects. Furthermore, the results of our in vivo experiments confirmed the neuroprotective effects of shXIST and miR-199a-3p against MPTP-induced brain injuries, and the Parkinson's disease behavioural symptoms were effectively alleviated upon shXIST or miR-199a-3p treatment. In summary, the results of the present study showed that lncRNA XIST sponges miR-199a-3p to modulate Sp1 expression and further accelerates Parkinson's disease progression by targeting LRRK2.