An integrated analysis of the competing endogenous RNA network associated of prognosis of stage I lung adenocarcinoma.

BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD). METHODS: Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001). CONCLUSIONS: This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.

Transformation of HBCDs by Rhodococcus sp. stu-38.

1,2,5,6,9,10-Hexabromocyclododecanes (HBCDs) are brominated flame retardants causing serious environmental pollution. HBCDs in the environment could be transformed to various products. Identification of transformation products has been performed using various mass-spectrometric techniques. However, bacterial transformation of HBCDs yielding low-level products was not well studied. In this paper, a Rhodococcus strain stu-38 which could stereoselectively transform HBCDs in mineral salt medium, seawater, and growth medium was isolated. Seven potential biotransformation products of HBCDs were identified by using GC-MS. These products, including brominated alkenes, dibromocyclododecadiene and bromocyclododecatriene; brominated alkenols, bromocyclododecadienol and bromocyclododecatrienol; fully debrominated compounds, cyclododecadiendiol, 1,2-epoxy-5,9-cyclododecadiene, and cyclododecadienol, were presented in rather low level which could lead to false negative results. The low-level transformation products should not be ignored because their toxicity was less assessment. This research highlighted identification of the low-level transformation products to reveal the complicated stereoselective biotransformation of HBCDs.

Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells.

Phenoxybenzamine hydrochloride (PHEN) is a selective antagonist of both α-adrenoceptor and calmodulin that exhibits anticancer properties. The aim of this study was to explore the anti-tumor function of PHEN in glioma. Cell proliferation assay was used to assess glioma cell growth. Migration and invasion capacity of glioma cells was monitored by wound-healing and transwell assay, respectively. Neurosphere formation test was adopted for the tumorigenesis of glioma cells, which was also confirmed by soft agar cloning formation test in vitro and a nude mouse model in vivo. Finally, we explored the potential pathway utilized by PHEN using Western blot and immunofluoresce staining. PHEN exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.

RNA interference against TMEM97 inhibits cell proliferation, migration, and invasion in glioma cells.

Gliomas are the most common form of primary brain tumor in the adult central nervous system. Altered expression and prognostic value of transmembrane protein 97 (TMEM97) has been recently reported in different types of human tumors. However, the association of TMEM97and glioma is poorly defined. Here, we reported that TMEM97 was significantly increased in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM97 levels were progressively increased with increasing histologic tumor grade in glioma. Higher TMEM97 expression level was correlated with shorter survival time of patients with glioma. Downregulation of TMEM97 through RNA interference inhibited cell proliferation and G1/S transition in two glioma cell lines, U87 and U373. More importantly, TMEM97 silencing induced a significant decrease in the expression of G1/S transition key regulators, cyclin D1, cyclin E, CDK2, and CDK4. Additionally, downregulation of TMEM97 in glioma cells notably repressed cell migration and cell invasion. Further analysis suggested that the decreased invasion was associated with alterations in EMT markers, including E-cadherin, ß-catenin, and Twist. Since expression of TMEM97 seems to be associated with the oncogenic potential of glioma, and suppression of its expression can inhibit cancer cell growth and metastasis, TMEM97 may be a potential therapeutic target in human glioma.

Enumeration and Molecular Characterization of Circulating Tumor Cell Using an Epithelial Cell Adhesion Molecule/Vimentin/Epidermal Growth Factor Receptor Joint Capture System in Lung Cancer.

Background: Detection rate and isolation yield of circulating tumor cells (CTCs) are low in lung cancer with approaches due to CTC invasiveness and heterogeneity. In this study, on the basis of the epithelial cell adhesion molecule (EpCAM) phenotype, markers of vimentin and epidermal growth factor receptor (EGFR) phenotype were added to jointly construct a precise and efficient CTC capture system for capture of lung cancer CTCs. Methods: A CTC capture system combined with EpCAM lipid magnetic bead (Ep-LMB)/vimentin lipid magnetic bead (Vi-LMB)/EGFR lipid magnetic bead (EG-LMB) was constructed, and its performance was tested. The amount of CTC captured in the blood of patients with lung cancer was detected by immunofluorescence identification and analyzed for clinical relevance. Results: The constructed CTC capture system has low cytotoxicity. The capture efficiency of lung cancer cells in phosphate belanced solution (PBS) system was 95.48%. The capture efficiency in the blood simulation system is 94.55%. The average number of CTCs in the blood of patients with lung cancer was 9.73/2 mL. The quantity distribution of CTCs is significantly correlated with tumor staging and metastasis. The area under the curve (AUC) of CTCs for the diagnosis of lung cancer was 0.9994 (95% CI = 0.9981-1.000, P < .0001). The cutoff value was 4.5/2 mL. The sensitivity was 99.39%, and the specificity was 96.88%. Conclusion: The EpCAM/vimentin/EGFR combined capture system has feasibility and high sensitivity in the detection of lung cancer CTC typing, which can be used as an auxiliary diagnostic indicator for lung cancer and is expected to promote the clinical application of CTCs.

LncRNA PRKCA-AS1 promotes LUAD progression and function as a ceRNA to regulate S100A16 by sponging miR-508-5p.

Objective: This study aimed to elucidate the underlying mechanism of LncRNA PRKCA-AS1 in lung adenocarcinoma (LUAD). Methods: The expression of LncRNA PRKCA-AS1, miR-508-5p and S100A16, in LUAD tissues or cell lines (NCI-H520 and H1299) was analyzed with qRT-PCR. The clinical diagnostic value of LncRNA PRKCAAS1, miR-508-5p and S100A16 in LUAD were analyzed by receptor operating characteristic (ROC) curve. Then we knockdown or overexpression of PRKCAAS1 in NCI-H520 and H1299 cells, and the cell function test was applied to detect the activity and metastasis level of cells in different transfection groups. Then Pearson correlation analysis was used for the correlation between miR-508-5p and PRKCA-AS1. The dual-luciferase reporter experiment and CHIRP analysis was conducted to verify the target binding relationship of PRKCA-AS1, miR-508-5p or S100A16. FISH assay analyzed the colocalization of PRKCA-AS1 and miR-508-5p in NCI-H520 and H1299 cells. Rescue experiment and tumorigenesis experiment in nude mice further explore the regulatory mechanisms of LncRNA PRKCA-AS1, miR-508-5p and S100A16 on LUAD progression in vitro and in vivo. Results: From the results, PRKCA-AS1 and S100A16 were up-regulated in LUAD tissues, while miR-508-5p was downregulated compared with the adjacent tissues. And gain-of-function revealed that PRKCA-AS1 knock-down apparently suppressed the cell proliferation and metastasis, whereas miR-508-5p inhibitors or S100A16 overexpression showed a opposite effect. In addition, there is evidence that PRKCA-AS1, miR-508-5p and S100A16 have a targeted regulatory relationship. Moreover, rescue experiment and tumorigenesis experiment in nude mice further confirmed that LncRNA PRKCA-AS1 regulates S100A16 through sponging miR-508-5p to regulate LUAD progression in vitro and in vivo. Conclusion: These results demonstrated that LncRNA PRKCA-AS1 might regulate LUAD by acting as a ceRNA via sponging miR-508-5p and regulating S100A16 expression, indicating that manipulation of PRKCA-AS1 might be a potential therapeutic strategy in LUAD.

Novel insights into aerobic 17ß-estradiol degradation by enriched microbial communities from mangrove sediments.

Various persistent organic pollutants (POPs) including estrogens are often enriched in mangrove regions. This research investigated the estrogens pollution levels in six mangroves located in the Southern China. The estrogen levels were found to be in the range of 5.3-24.9 ng/g dry weight, suggesting that these mangroves had been seriously contaminated. The bacterial communities under estrogen stress were further enriched by supplementing 17ß-estradiol (E2) as the sole carbon source. The enriched bacterial communities showed an excellent E2 degradation capacity > 95 %. These communities were able to transform E2 into estrone (E1), 4-hydroxy-estrone, and keto-estrone, etc. 16 S rDNA sequencing and metagenomics analysis revealed that bacterial taxa Oleiagrimonas, Pseudomonas, Terrimonas, and Nitratireductor etc. were the main contributors to estrogen degradation. Moreover, the genes involved in E2 degradation were enriched in the microbial communities, including the genes encoding 17ß-hydroxysteroid dehydrogenase, estrone 4-hydroxylase, etc. Finally, the analyses of functional genes and binning genomes demonstrated that E2 was degraded by bacterial communities via dehydrogenation into E1 by 17ß-hydroxysteroid dehydrogenase. E1 was then catabolically converted to 3aα-H-4α(3'-propanoate)- 7aß-methylhexahydro-1,5-indanedione via 4,5-seco pathway. Alternatively, E1 could also be hydroxylated to keto-estrone, followed by B-ring cleavage. This study provides novel insights into the biodegradation of E2 by the bacterial communities in estrogen-contaminated mangroves.

The association between maternal diabetes and neonatal seizures: a nested case-Control study.

Aim: We aimed to evaluate the association of pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) with neonatal seizures during neonatal hospitalization. Methods: In this nested case-control study, all data were collected from the data files of the National Vital Statistics System (NVSS) 2016-2021. Considering the effect of confounders, we used the propensity-score matching (PSM; case:control = 1:4) method to select the study population. The outcome was considered the occurrence of neonatal seizures. Univariate and multivariate logistic regression analyses were adopted to assess the association of PGDM and GDM with neonatal seizures. We also conducted stratified analyses according to gestational age, birthweight, 5 min Apgar score, and maternal age to explore the potential disparities. Results: After using the PSM method, a total of 6,674 cases of neonatal seizures and 26,696 controls were included. After adjusting for covariates, PGDM was associated with an increased risk of neonatal seizures [odds ratio (OR) = 1.51, 95% confidence interval (CI): 1.15-1.98], whereas the association between GDM and neonatal seizures is not statistically significant. In addition, the correlation between PGDM and increased risk of neonatal seizures was observed in neonates with a gestational age of 37-42 weeks and ≥42 weeks, with a 5 min Apgar score of ≥7, and with a maternal age of ≤40 years. Conclusion: PGDM was found to be closely associated with an increased risk of neonatal seizures. The findings of our study indicated that neonatologists should consider monitoring the incidence of neonatal seizures in neonates born to mothers with PGDM.

miR-508-5p serves as an anti-oncogene by targeting S100A16 to regulate AKT signaling and epithelial-mesenchymal transition process in lung adenocarcinoma cells.

BACKGROUND: Our aim was to expose the effect of miR-508-5p on the developmental and biological behaviour of lung adenocarcinoma (LUAC). METHODS: The KM plotter was used to analyze the survival significance of miR-508-5p and S100A16 expression in LUAC patients. qRT-PCR was performed to detect the expression of miR-508-5p and S100A16 in LUAC tissue and LUAC cell lines. CCK8, colony formation and Transwell were performed to evaluate the effects of miR-508-5p and S100A16 on cell proliferation and metastasis. Dual luciferase reporter assay was used to verify that S100A16 were targets of miR-508-5p. Western blot analysis was performed to analyze protein expression. RESULTS: Results showed that low miR-508-5p expression in LUAC tissues indicated poorer overall survival of LUAC patients and miR-508-5p was downregulated in LUAC cell lines compared to the normal human lung epithelial cell line. miR-508-5p mimics could inhibit A549 cell proliferation and metastasis abilities, while miR-508-5p Antagomir showed the opposite effect. We identified S100A16 as one direct target of miR-508-5p, and rescuing S100A16 expression could reverse the effect of miR-508-5p mimics on A549 cell proliferation and metastasis. miR-508-5p could involve the coordination of AKT signaling and epithelial-mesenchymal transition (EMT) progress using western-blot assays and rescuing S100A16 expression could reverse the inhibited AKT signaling and EMT progress induced by miR-508-5p mimics. CONCLUSIONS: We found that miR-508-5p targeted S100A16 to regulate AKT signaling and EMT progress in A549 cells, resulting in impaired cell proliferation and metastasis activity, suggesting that miR-508-5p might be a promising therapeutic target and an important diagnostic and prognostic marker for improved LUAC therapeutic schedule.

A targeted siRNA-loaded PDL1-exosome and functional evaluation against lung cancer.

BACKGROUND: As an endocytic nanosicle involved in intercellular communication, an exosome can efficiently deliver drugs from one cell to another and deliver therapeutic short interfering RNA (siRNA) to target cells. This is conducive to gene therapy for cancers. In this study, an exosome was used as the siRNA-loaded substrate to prepare a targeted siRNA-loaded PD-L1 exosome and evaluate its function against lung cancer. METHODS: The optimal preparation process and binding ratio of the targeted nanovesicle/siRNA complex was determined by detecting the particle size, potential, and other physical parameters in combination with cell binding and uptake capacity of exosome complexes. The biological cell behavior of targeted exosome nanosicles was evaluated through cytotoxicity, apoptosis, and the cell uptake capacity. RESULTS: A targeted exosome nanovesicle capable of loading siRNA and characterized with low toxicity, high loading rate, and the ability to be used for targeted tumor cell gene therapy was constructed. CONCLUSION: The PD-L1 targeting exosome can be used as an efficient siRNA delivery carrier, which is an efficient and safe nanocarrier for tumor targeted gene therapy.

Survival outcomes for patients with four treatments in stages I-III esophageal squamous cell carcinoma: a SEER analysis.

BACKGROUND: Esophageal cancer (EC) is globally acknowledged as one of the most common malignancies among all gastrointestinal cancers. Furthermore, in Eastern Asia, squamous cell carcinoma is the main pathological type of EC. There are different treatments for esophageal squamous cell carcinoma (ESCC), but there is still a lack of large-sample analysis of prognosis among different treatments, especially for different tumor stages. The analysis of the prognosis of ESCC patients with different treatments may be helpful to choose the treatment methods for different stages ESCC. METHODS: A total of 3,346 patients with pathological ESCC between 1976 and 2016 were derived from the Surveillance, Epidemiology, and End Results (SEER) database. All clinical factors associated with prognosis were collected and analyzed to achieve the difference of prognosis among different treatments in ESCC patients, such as ages, sex, race, tumor grade, anatomic location and so on. Kaplan-Meier and Cox proportional hazard analysis were used to compare survival of different treatments in ESCC patients with stage I-III. RESULTS: The overall survival (OS) in all ESCC patients who had received surgery and surgery plus radiation therapy or/and chemotherapy are superior than that had not received any treatments and radiation therapy or/and chemotherapy. The OS in ESCC patients with stage I who had received surgery and surgery plus radiation therapy or/and chemotherapy are superior than that had not received any treatments and radiation therapy or/and chemotherapy. The OS in ESCC patients with stage II/III who had received surgery and surgery plus radiation therapy or/and chemotherapy are superior than that in other groups. Age, race and grade as an independent predictive factor for survival (P<0.05). A nomogram model was constructed to show surgery group had better 1-, 3- and 5-year OS than radiation therapy or/and chemotherapy group (OS: 78.5% vs. 59.2%, 37.9% vs. 18.4%, 16.9% vs. 6.1%). CONCLUSIONS: Surgery is still the first choice for all ESCC patients with stage I-III. Radiotherapy and chemotherapy could improve the survival rate in ESCC patients with stage II-III who have received surgery.

LncRNA WT1-AS/miR-494-3p Regulates Cell Proliferation, Apoptosis, Migration and Invasion via PTEN/PI3K/AKT Signaling Pathway in Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common malignancies with the highest morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) are recently recognized as noteworthy regulators of different tumors, counting NSCLC. However, the biological functions and regulatory mechanism of lncRNA WT1-AS in NSCLC progression still stay uninvestigated. METHODS: WT1-AS and miR-494-3p levels in NSCLC cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). In the current study, the regulatory effects of WT1-AS/miR-494-3p axis on cellular behaviors of NSCLC cell lines (A549 and NCI-H1975) were evaluated by a variety of methods. Cell counting kit-8 (CCK-8) and EDU assays were adopted to assess NSCLC cell proliferation. Tunnel staining and flow cytometry assay were applied to determine cell apoptosis and cell cycle distribution. Besides, cell migration and invasion abilities were analyzed by performing wound healing and transwell assays. Meanwhile, the levels of key proteins related to NSCLC cell apoptosis and PTEN/PI3K/AKT pathway were examined using Western blot assay. In addition, luciferase reporter assays were used to determine the interaction between WT1-AS and miR-494-3p or miR-494-3p and PTEN. RESULTS: Visibly downregulated WT1-AS in NSCLC cell lines was obtained from Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and further verified by performing RT-qPCR. Besides, miR-494-3p was the downstream target gene of WT1-AS and obviously upregulated miR-494-3p in NSCLC cell lines was confirmed. WT1-AS overexpression suppressed cell proliferation, migration and invasion abilities while enhanced cell apoptosis of A549 and NCI-H1975 cells. Furthermore, upregulation of miR-494-3p distinctly reversed these inhibitory effects of WT1-AS overexpression on the tumorigenesis and progression of NSCLC. In addition, WT1-AS promoted PTEN expression and thereby inhibited activation of PI3K/AKT pathway by sponging miR-494-3p. CONCLUSION: To conclude, lncRNA WT1-AS impeded cell proliferation, migration, invasion but accelerated cell apoptosis via negatively regulating miR-494-3p to mediate PTEN/PI3K/AKT pathway in NSCLC.

lncRNA LEF1-AS1 Promotes Malignancy in Non-Small-Cell Lung Cancer by Modulating the miR-489/SOX4 Axis.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) could participate in diverse cancers. Among these, lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was recently identified as an oncogenic lncRNA, but little is known about its function in non-small-cell lung cancer (NSCLC). In the present study, we found that LEF1-AS1 was markedly upregulated in lung cancer tissues and could promote NSCLC cell proliferation and migration in vivo and in vitro. LEF1-AS1 could bind with miR-489 and further negatively regulate miR-489 to promote SRY-related HMG box transcription factor 4 (SOX4) expression. In conclusion, these data suggested that LEF1-AS1 promoted NSCLC tumorigenesis dependent on the miR-489-SOX4 axis and implicated the potential application of LEF1-AS1 for the prognosis and treatment of NSCLC.

18F-FDG PET-CT metabolic findings can predict the short-term curative effects in esophageal cancer.

OBJECTIVE: 18F-FDG PET-CT is a noninvasive approach extensively used to assess the therapeutic results and give a prognosis for esophageal cancer. This study is focused on examining the predictive value of metabolic tumor volume (MTV) and pre-treatment maximal standardized uptake value (SUVmax) of short-term curative effects demonstrated in patients with esophageal cancer. METHODS: This study carried out a retrospective analysis of 98 patients diagnosed with esophageal cancer who received treatment by radiotherapy or a combination of chemotherapy and radiotherapy in the Second Affiliated Hospital of Fujian Medical University. 18F-FDG PET-CT scan was carried out prior to the treatment. PET/CT images before treatment were evaluated by two high-level professional doctors as a double-blind method. MTV and SUVmax values were averaged and confirmed. In 1 to 3 months after the treatment, a deputy director of PET/CT center with much experience and a radiotherapist assessed the curative effect of all patients in line with the Response Evaluation Criteria in Solid Tumor (RECIST). RESULTS: No considerable difference in SUVmax and MTV was observed between the two groups in cancer site, gender, age, or differential extent. In addition, there was a significant correlation between SUVmax and lesion length, lymph node metastasis, depth of invasion, and clinical stage. SUVmax was positively correlated to depth of invasion, lymph node metastasis, MTV, lesion length, and clinical stage. The value of effective rate was up to 67.3% (66/98). There was a negative correlation between MTV as well as SUVmax, and curative effects in the short term, whereas the curative effects of MTV exceeded that of SUVmax. CONCLUSION: MTV and SUVmax before treatment serve to forecast curative effects in the short term of radiotherapy or combination of chemotherapy and radiotherapy for patients with esophageal cancer. MTV had a greater predictive effect than SUVmax.

Knockdown of TMEM45A inhibits the proliferation, migration and invasion of glioma cells.

Gliomas are the most common and aggressive type of primary adult brain tumor. Although high expression and prognostic value of TMEM45A has been recently reported in various types of human tumors, the association of TMEM45A expression and glioma is still unknown. Here, we reported that TMEM45A was significantly overexpressed in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM45A mRNA levels were gradually increased with the increasing severity of histological grade of glioma. Moreover, high TMEM45A expression level was correlated with short survival time of glioma patients. Down-regulation of TMEM45A in two glioma cell lines, U251 and U373 by transected with TMEM45A siRNA resulted in a significant reduction of cell proliferation and G1-phase arrest. Additionally, we found that suppressing of TMEM45A expression in glioma cells remarkably suppressed cell migration and cell invasion. More importantly, TMEM45A siRNA treatment significantly down-regulated the proteins promoting cell cycles transition (Cyclin D1, CDK4 and PCNA) and cell invasion (MMP-2 and MMP-9), which indicted a possible mechanism underlying its functions on glioma. In summary, our study suggests that TMEM45A may work as an oncogene and a new effective therapeutic target for glioma treatment.

The transducible TAT-RIZ1-PR protein exerts histone methyltransferase activity and tumor-suppressive functions in human malignant meningiomas.

Malignant meningiomas are a rare meningioma subtype and tend to have post-surgical recurrence. Significant endeavors have been taken to identify functional therapeutic targets to halt the growth of this aggressive cancer. We have recently discovered that RIZ1 is downregulated in high-grade meningiomas, and RIZ1 overexpression inhibits proliferation while promoting cell apoptosis of the IOMM-Lee malignant meningioma cell line. In this report, we show that the N-terminal PR domain of RIZ1 alone possessed growth-inhibitory activity and anticancer activity in primary human meningioma cells. Interestingly, the effects seem to be dependent on differential RIZ1 protein levels. Transducible TAT-RIZ1-PR protein could also inhibit meningioma tumor growth in nude mice models. We further demonstrate that PR protein exerts histone methyltransferase activity. A microarray analysis of TAT-RIZ1-PR-treated human malignant meningioma cells reveals 969 differentially expressed genes and 848 alternative splicing exons. Moreover, c-Myc and TXNIP, two putative downstream targets of H3K9 methylation, may be involved in regulating RIZ1 tumor-suppressive effects. The reciprocal relationship between RIZ1 and c-Myc was then validated in primary meningioma cells and human tumor samples. These findings provide insights into RIZ1 tumor suppression mechanisms and suggest that TAT-RIZ1-PR protein is a potential new epigenetic therapeutic agent for advanced meningiomas.

Differential lncRNA expression profiles in recurrent gliomas compared with primary gliomas identified by microarray analysis.

Glioma, especially high-grade glioma, is highly malignant with high rate of recurrence and poor prognosis. The mechanisms of glioma progression and recurrence have not been elucidated. Previous studies showed that long non-coding RNAs (lncRNAs) involved in the development and progression of glioma. However, the roles of lncRNAs in the recurrence of glioma remain unknown. We use high throughput microarray to screen the differentially expressed lncRNAs and mRNAs in recurrence gliomas compared with primary gliomas. We found a total of 1,111 lncRNAs were differentially expressed in recurrent group. Among these, 639 lncRNAs were up-regulated, while 472 lncRNAs were down-regulated (fold Change ≥2.0). GO (Gene ontology) and pathway analysis revealed that the potential functions of differentially expressed lncRNAs were closely connected with the processes of cancer progression and pathogenesis. LncRNA classification and subgroup analysis further identified three important clusters of differentially expressed lncRNA-mRNA pairs which have potential gene regulatory functions. This study for the first time showed abundant differentially expressed lncRNAs in recurrent gliomas. Some lncRNAs may play important roles in glioma recurrence, such as previously reported H19, CRNDE, HOTAIRM1 or unreported AC016745.3, XLOC_001711, RP11-128A17.1. Moreover, this study set a basis for future researches on specific lncRNA which may contribute to the recurrence of glioma. Further studies on these lncRNAs will help to elucidate the mechanism of glioma recurrence at genetic level and find therapeutic targets for glioma patients.