[Research progress of chemerin in polycystic ovary syndrome].

As a multifunctional adipokine, chemerin plays a crucial role in various pathophysiological processes through endocrine and paracrine manner. It can bind to three known receptors (ChemR23, GPR1 and CCRL2) and participate in energy metabolism, glucose and lipid metabolism, and inflammation, especially in metabolic diseases. Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, which seriously affects the normal life of women of childbearing age. Patients with PCOS have significantly increased serum levels of chemerin and high expression of chemerin in their ovaries. More and more studies have shown that chemerin is involved in the occurrence and development of PCOS by affecting obesity, insulin resistance, hyperandrogenism, oxidative stress and inflammatory response. This article mainly reviews the production, subtypes, function and receptors of chemerin protein, summarizes and discusses the research status of chemerin protein in PCOS from the perspectives of metabolism, reproduction and inflammation, and provides theoretical basis and reference for the clinical diagnosis and treatment of PCOS.

Neuronal MeCP2 in the dentate gyrus regulates mossy fiber sprouting of mice with temporal lobe epilepsy.

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system.

Will climate warming of terrestrial ecosystem contribute to increase soil greenhouse gas fluxes in plot experiment? A global meta-analysis.

One of the main manifestations of global climate change is its profound impact on the emission of greenhouse gases from terrestrial soil. Numerous field warming experiments have explored the effects of different temperature rise intensities and durations on soil greenhouse gas fluxes in the growing season of different terrestrial ecosystems. However, the results were inconsistent due to the variations in vegetation, soil, and climatic conditions in different ecosystems. In the present work, we carried meta-analysis to synthesize 99 datasets from 52 field warming experiments in growing seasons of terrestrial ecosystems to evaluate the response of soil greenhouse gas fluxes to global warming. The results showed that warming greatly stimulated soil CO2 in temperate forest and farmland by 12.64% and 25.57%, respectively, significantly increased soil N2O emissions in grassland (27.23%), farmland (44.33%), and shrubland (223.36%), and increased soil CH4 uptake by 57.81% in grasslands. However, no significant impact on the greenhouse gas fluxes in other ecosystems was observed. Generally, short-and medium-term (≤ 3 years) warming can promote soil greenhouse gas fluxes. Also, low temperature and low-medium temperature (≤ 2 °C) significantly promoted N2O emission and CH4 absorption, and medium temperature (2-4 °C) considerably assisted CO2 flux, but high temperature (> 4 °C) had no significant effect on greenhouse gas flux. Our results demonstrated that soil greenhouse gas fluxes in terrestrial ecosystems during the growing season do not increase linearly with the increasing climate warming, and it is still uncertain whether there is acclimatization to long-term climate warming.

Transbrachial Access for Transcatheter Closure of Paravalvular Leak Following Prosthetic Valve Replacement.

Background: Transcatheter closure of paravalvular leak (PVL) has evolved into an alternative to surgery in high-risk patients. In this study, we introduce a new access for transcatheter closure of PVL and seek to evaluate the feasibility and safety of this access. Methods: We retrospectively analyzed patients undergoing transbrachial access for transcatheter mitral or aortic PVL closure (August 2017-November 2019) at our hospital. All patients underwent puncture of the brachial artery under local anesthesia. Results: The study population included 11 patients, with an average age of 55.91 ± 14.82 years. Ten out of 11 patients were successfully implanted with devices via the brachial artery approach, and one patient was converted to the transseptal approach. The technical success rate of transbrachial access was 90.9%. Mean NYHA functional class improved from 3.1 ± 0.5 before the procedure to 1.9 ± 0.5 after PVL closure. Severe paravalvular regurgitation (PVR) in five patients and moderate PVR in six patients prior to the procedure were significantly reduced to mild in four patients and none in seven patients after the procedure. Complications included one case of pseudoaneurysm and one case of moderate hemolysis aggravation after closure. One patient had an unknown cause of sudden death within 24 h after the procedure. The half-year mortality rate during follow-up was 9.1% (1/11). Conclusions: Transbrachial access for transcatheter closure of PVL may be a feasible and safe treatment and should include well-selected patients. It has several potential advantages of simplifying the procedure process and reducing postprocedural bed rest time.

Circular RNAs: Promising biomarkers for cancer diagnosis and prognosis.

Circular RNAs (circRNAs), a group of non-coding RNA characterized by the presence of covalent bonds linking 3' and 5' ends, act as miRNA sponges to participate in the tumorigenesis. Being stable, conserved and cell- or tissue-specific, circRNAs have shown their potentials as molecular markers for cancer. Convenient and noninvasive approaches may be developed based on the roles of circRNAs to diagnose or predict the prognosis of tumors. Although most of the potential mechanisms are not entirely clear, circRNAs have shown a universal and critical role in regulating cellular processes of cancers. This review summarized the classification, formation, characteristics, detection, and biological functions of circRNAs. We proposed the possibility of using circRNAs as biomarkers for cancer diagnosis, treatment and prognosis.

Status epilepticus induced Gadd45b is required for augmented dentate neurogenesis.

In animal models with temporal lobe epilepsy (TLE), the status epilepticus (SE) leads to a dramatic increase in number of newly born neuron in the subgranular zone (SGZ) of dentate gyrus. How the SE confers a modulation in the dentate neurogenesis is mostly unknown. Gadd45b is involved in epigenetic gene activation by DNA demethylation. This study was performed to present a novel mechanism underling SE-induced dentate neurogenesis. A transient induction (12 hrs to 3 days) of Gadd45b was observed in dentate gyrus of mice after pilocarpine-induced SE. Labeling the dividing cells with BrdU, we next found that the induction of Gadd45b was required to increase the rate of cell proliferation in the dentate gyrus at 7 and 14 days after SE. Afterward, the DNA methylation levels for candidate growth factor genes critical for the adult neurogenesis were assayed with Sequenom MassARRAY Analyzer. The results indicated that Gadd45b was necessary for SE-induced DNA demethylation of specific promoters and expression of corresponding genes in the dentate gyrus, including brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF-2). Using Timm staining, we further suggested that SE-induced Gadd45b might contribute to the subsequent mossy fiber sprouting (MFS) in the chronically epileptic hippocampus via epigenetic regulation of dentate neurogenesis at early stage after SE. Together, Gadd45b links pilocarpine-induced SE to epigenetic DNA modification of secreted factors in the dentate gyrus, leading to extrinsic modulation on the neurogenesis.

Personalized Three-Dimensional Printing and Echoguided Procedure Facilitate Single Device Closure for Multiple Atrial Septal Defects.

BACKGROUND: To evaluate the feasibility of using a single device to close multiple atrial septal defects (ASDs) under the guidance of transthoracic echocardiography (TTE) and with the aid of three-dimensional (3D) printing models. METHODS: Sixty-two patients with multiple ASDs were retrospectively analyzed. Thirty of these patients underwent TTE-guided closure (3D printing and TTE group) after a simulation of occlusion in 3D printing models. The remaining 32 patients underwent ASD closure under fluoroscopic guidance (conventional group). Closure status was assessed immediately and at 6 months after device closure. RESULTS: Successful transcatheter closure with a single device was achieved in 26 patients in the 3D printing and TTE group and 27 patients in the conventional group. Gender, age [18.8 ± 15.9 (3-51) years in the 3D printing and TTE group; 14.0 ± 11.6 (3-50) years in the conventional group], mean maximum distance between defects, prevalence of 3 atrial defects and large defect distance (defined as distance ≥7 mm), and occluder size used were similarly distributed between groups. However, the 3D printing and TTE group had lower frequency of occluder replacement (3.8% vs 59.3%, p < 0.0001), prevalence of mild residual shunts (defined as <5 mm) immediately (19.2% vs 44.4%, p < 0.05) and at 6 months (7.7% vs 29.6%, p < 0.05) after the procedure, and cost (32960.8 ± 2018.7 CNY vs 41019.9 ± 13758.2 CNY, p < 0.01). CONCLUSION: The combination of the 3D printing technology and ultrasound-guided interventional procedure provides a reliable new therapeutic approach for multiple ASDs, especially for challenging cases with large defect distance.

High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial-mesenchymal transition in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a more frequent subtype of lung cancer and most cases are discovered in the late stages. The proliferation and metastasis of LUAD are pivotal for disease progression. Despite unremitting deeper understanding of LUAD biology, the mechanisms involved in the proliferation and metastasis of LUAD remain unclear. The objective of our article was to inquiry the expression and the function of keratin 6C (KRT6C) in LUAD cells. METHODS: First, the expression level and prognostic value of KRT6C in LUAD tissues were analyzed on the basis of the data acquired from TCGA database. Through qRT-PCR, the expression level of KRT6C on LUAD cell lines (A549, H1299, PC-9) and human normal lung cell line MRC-5 was tested. After that, CCK8 and colony formation assays was utilized to detect cell proliferation. In addition, to explore the influence of KRT6C on LUAD migration and invasion ability, scratch wound healing and transwell assays were utilized. Through western blotting, the protein expression levels of KRT6C, PCNA, E-cadherin, N-cadherin, Snail and Vimentin were detected. RESULTS: The outcomes revealed that KRT6C was highly expressed in LUAD tissues and cell lines. Besides, elevated level of KRT6C was related to worse prognosis in LUAD patients. Ablation of KRT6C restrained proliferation, migration and invasion of A549 cells. KRT6C deficiency augmented the expression of E-cadherin as well as reduced the expression of N-cadherin, Snail and Vimentin. CONCLUSION: Above all, these consequences indicated that depletion of KRT6C suppressed A549 cell proliferation, migration and invasion, which might be achieved by regulating EMT. In general, KRT6C is identified as a potential therapeutic target for LUAD.

Downregulation of lysyl oxidase-like 4 LOXL4 by miR-135a-5p promotes lung cancer progression in vitro and in vivo.

Aberrant microRNAs are widely identified in multiple cancers, including lung cancer. miR-135a-5p can function as a significant tumor regulator in diverse cancers via impacting multiple genes in oncogenic pathways. Nevertheless, the biological role of miR-135a-5p in lung cancer is poorly known. Here, we investigated its function in lung cancer. As exhibited, miR-135a-5p was elevated in lung cancer cells in contrast to BEAS-2B cells. Then, we inhibited miR-135a-5p expression by transfecting LV-anti-miR-135a-5p into lung cancer cells. As displayed, miR-135a-5p was obviously reduced in A549 and H1299 cells. Knockdown of miR-135a-5p repressed lung cancer cell growth and cell proliferation. Meanwhile, cell colony formation capacity was depressed, cell apoptosis was enhanced and cell cycle progression was blocked in G1 phase by inhibition of miR-135a-5p in vitro. Additionally, the migration and invasion of A549 and H1299 cells was strongly depressed by LV-anti-miR-135a-5p. For another, by using informatics analysis, lysyl oxidase-like 4 (LOXL4) was speculated as the downstream target of miR-135a-5p. We validated their direct correlation and moreover, overexpression of miR-135a-5p restrained LOXL4 levels in lung cancer cells. Subsequently, we proved that miR-135a-5p promoted lung cancer development via targeting LOXL4 by carrying out the in vivo assays. Taken these together, our study revealed miR-135a-5p might be indicated as a perspective for lung cancer via targeting LOXL4.

miR-210 promotes lung adenocarcinoma proliferation, migration, and invasion by targeting lysyl oxidase-like 4.

Accumulating evidence has revealed that various microRNAs are deregulated and involved in lung cancer development and metastasis. miR-210 is implicated in several cancer progression. However, the detailed biological function and role of miR-210 in lung adenocarcinoma remains unclear. Our current study was aimed to investigate the mechanism of miR-210 in lung adenocarcinoma progression. We observed that miR-210 was significantly upregulated in lung cancer cell lines (A549 and H1650) in comparison to BEAS-2B cells. In addition, we found that miR-210 was greatly elevated in lung adenocarcinoma tissues. Then, it was shown that overexpression of miR-210 was able to promote lung cancer cell proliferation and colony formation ability while inhibitors of miR-210 exhibited a reversed phenomenon. Subsequently, A549 and H1650 cell migration and invasion capacity were obviously restrained by miR-210 inhibition whereas induced by miR-210 mimics. Lysyl oxidase-like 4 (LOXL4), a member of the secreted copper-dependent amine oxidases has been found to be increased or decreased in different cancer types. Here, we confirmed that LOXL4 could serve as a downstream target of miR-210 and miR-210 promoted lung cancer progression via targeting LOXL4. In A549 and H1650 cells, knockdown of LOXL4 dramatically repressed lung cancer cell proliferation, migration, and invasion. In conclusion, our study implied that miR-210 might indicate a new perspective for lung cancer.

Long noncoding RNA CCAT2 functions as a competitive endogenous RNA to regulate FOXC1 expression by sponging miR-23b-5p in lung adenocarcinoma.

Long noncoding RNA (lncRNA) may regulate the process of tumor formation. Although lncRNA CCAT2 has been identified as a key point in many diseases, its pathophysiological mechanism in lung adenocarcinoma remains unknown. We measured the expression level of CCAT2 in lung adenocarcinoma cells and normal lung epithelial cell line BEAS-2B by quantitative real-time polymerase chain reaction (qRT-PCR). As well, cell migration and proliferation were detected by transwell detection and CCK8 assay. At the same time, the new target point of CCAT2 was confirmed with bioinformatics analysis and dual-luciferase reporter assay. In addition, potential mechanisms were studied by Western blot analysis and RNA immunoprecipitation (RIP) analysis. The expression of CCAT2 was upregulated obviously in lung adenocarcinoma cells. Cell function analysis showed that upregulation of CCAT2 significantly promoted cell proliferation and migration, and reduction of CCAT2 inhibited cell migration and proliferation. In addition, CCAT2 positively regulated the expression of FOXC1 by competitive binding with miR-23b-5p. These findings indicated that CCAT2 may act as a competitive endogenous RNA (ceRNA) to regulate FOXC1 expression by competitively binding miR-23b-5p in lung adenocarcinoma.

Safety and efficacy of percutaneous closure of ruptured sinus of Valsalva aneurysm.

AIMS: The aim of this study was to evaluate the safety and efficacy of percutaneous closure in patients with a ruptured sinus of Valsalva aneurysm (RSVA). METHODS AND RESULTS: A total of 29 patients with RSVA were retrospectively enrolled in our study. All patients were successfully treated by percutaneous closure and had a complete closure at discharge; however, two patients had a trivial procedure-related aortic regurgitation (AR) after the procedure. On a mean follow-up of 29.7±23.8 months (range 1-83 months), the two procedure-related AR disappeared three months and two years after the procedure, respectively. Trivial residual shunt was found in one patient, sinus of Valsalva aneurysm ruptured again in one patient and trivial to moderate AR was found in two patients during the follow-up. CONCLUSIONS: In appropriately selected patients with RSVA, percutaneous closure is an attractive alternative to surgery with high technical success and good short-term and midterm outcomes; however, long-term follow-up is mandatory.

Long noncoding RNA LINC00961 inhibits cell proliferation and induces cell apoptosis in human non-small cell lung cancer.

Long noncoding RNAs (LncRNAs) have been identified in multiple human cancer types, including lung cancer. An increasing number of studies have indicated that lncRNAs can function as important gene regulators. However, the biological mechanism of LINC00961 in lung cancerremains poorly understood. In our current study, we recognized lncRNA LINC00961, and we observed that it was significantly reduced in human non-small cell lung cancer (NSCLC) tissues. LINC00961 was elevated by infecting LV-LINC00961, while decreased by LV-shLINC00961 in H226 and A549 cells. Furthermore, it was shown that LINC00961 overexpression greatly inhibited lung cancer cell proliferation, whereas downregulated LINC00961 induced cell proliferation. In addition, further experiments showed that restoration of LINC00961 could dramatically increase apoptotic ratios of NSCLC H226 and A549 cells, and knockdown of LINC00961 exhibited an opposite effect. Moreover, Western blot analysis showed that upregulation of LINC00961 repressed proliferating cell nuclear antigen expression and increased Bax expression, indicating that it acts as an important pro-apoptosis gene. Conversely, inhibition of LINC00961 induced proliferating cell nuclear antigen expression and restrained Bax protein levels. Taking these together, LINC00961 might play a tumor suppressive role in NSCLC progression, and it could serve as a novel prognostic biomarker in NSCLC diagnosis and treatment.

DNA methylation biomarkers for the occurrence of lung adenocarcinoma from TCGA data mining.

The development of lung cancer is a combination of multifactor, multistage, and multiple genetic alterations processes. DNA methylation is an important factor. Currently, the study on the genome-scale epigenetic modification for studying the pathogenesis of lung cancer is still lacking. Here, we aimed to identify the epigenetic modifications of lung cancer, thus to provide scientific basis for the personalized medicine, and research of classification screening for lung adenocarcinoma patients. The DNA methylation data, and the corresponding clinical information of lung adenocarcinoma samples were extracted from the Cancer Genome Atlas (TCGA) database. We explored the association of DNA methylation and gene transcription expression of lung adenocarcinoma by identifying the differentially expressed genes, DNA methylated locis, functional gene clusters, and the relevant genes associated with the survival. We identified 17 differentially expressed genes which had differentially methylated locis, 4 functional gene clusters regulated by methylation, and 522 genes, which were relevant to the survival time of patients. Our study suggested that methylation controlled the gene expression in a variety of ways, which had high/low expression and hyper-/hypo-methylation. Genes of different methylation status showed the different survival curve. The genes and methylated locis identified in this study could be potential biomarkers and therapeutic targets for lung adenocarcinoma.

H19 promotes non-small-cell lung cancer (NSCLC) development through STAT3 signaling via sponging miR-17.

LncRNAs can exhibit crucial roles in the development of multiple cancers, including non-small cell lung cancer (NSCLC). Currently, we investigated the role of lncRNA H19 in NSCLC. In our study, it was found that H19 was upregulated in A549 and H1299 cells compared to normal lung epithelial BEAS-2B cells. Meanwhile, we observed that miR-17 was downregulated in NSCLC cell lines. Inhibited H19 can suppress the growth, migration, and invasion of NSCLC cells and bioinformatics search was performed to predict the correlation between H19 and miR-17. Overexpression of miR-17 was able to inhibit the progression of NSCLC cells while reversely miR-17 inhibitors reversed this process. In addition, signal transducers and activators of transcription (STAT3), as an mRNA target of miR-17, was presented in our research. Moreover, we discovered that H19 demonstrated its biological functions via regulating miR-17 and STAT3 in vitro. Silencing H19 greatly increased STAT3 expression by sponging miR-19 in vitro. It was hypothesized that H19 may serve as a competing endogenous RNA (ceRNA) to modulate STAT3 by attaching miR-17 in lung cancer. In summary, our findings indicated that H19/miR-17/STAT3 axis participated in NSCLC development. H19 could be regarded as a significant prognostic biomarker in NSCLC progression.

The lncRNA MALAT1 contributes to non-small cell lung cancer development via modulating miR-124/STAT3 axis.

lncRNAs can exert many biological effects in several cancer types. MALAT1 is a kind of lncRNA which is greatly overexpressed in several tumors including non-small cell lung cancer (NSCLC). However, the mechanism of MALAT1 in NSCLC still remains unclear. In our current study, we concentrated on the biological mechanism of MALAT1 in NSCLC. It was observed that MALAT1 was significantly upregulated in five human NSCLC cells including A549, H23, H522, H1299, and H460 cells compared to normal bronchial epithelial cell line 16HBE cells. On the contrary, miR-124 was remarkably downregulated, which indicated a potential negative correlation between miR-124 and MALAT1. MALAT1 inhibition can increase miR-124 expression in A549 and H460 cells. In addition, miR-124 mimics were able to repress MALAT1 expression and miR124 inhibitors can promote MALAT1 levels. Then it was found that shMALAT1 can inhibit NSCLC cell proliferation, colony formation and apoptosis, which can be reversed by miR-124 inhibitors. Bioinformatic analysis predicted the correlation between miR-124 and MALAT1. In addition, STAT3 was found to be a novel mRNA target of miR-124. Downregulation of MALAT1 can inhibit NSCLC development by enhancing miR-124 and decreasing STAT3 expression. We speculated that MALAT1can act as a competing endogenous lncRNA (ceRNA) to modulate miR-124/STAT3 in NSCLC. Taken these together, we revealed that MALAT1/miR-124/STAT3 was involved in NSCLC development.

Long non-coding RNA LINC00968 acts as oncogene in NSCLC by activating the Wnt signaling pathway.

Long non-coding RNAs (lncRNAs) have played critical roles in a variety of cancers, including non-small cell lung cancer (N SCLC). In our study, we focused on the biological function and clinical significance of lncRNA LINC00968 in NSCLC. It was indicated that LINC00968 was significantly increased in LUAD tissues, LUSC tissues and NSCLC cells compared to their corresponding controls. Inhibition of LINC00968 was able to repress NSCLC growth, migration, and invasion in vitro while upregulation of LINC00968 reversed this process. Additionally, downregulation of LINC00968 induced apoptosis capacity of A549 cell. Apoptosis-related proteins BCL-2 were decreased and BAX was increased by knockdown of LINC00968, respectively. Meanwhile we observed that Wnt signaling pathway was involved in the LINC00968-induced NSCLC progression. Finally, in vivo tumor xenografts were established using A549 cells to detect the function of LINC00968 in NSCLC tumorigenesis. Silencing LINC00968 greatly inhibited NSCLC tumor progression, which was consistent with the in vitro tests. In conclusion, we have uncovered that LINC00968 could be regarded as a novel prognostic biomarker and therapeutic target in NSCLC diagnosis and treatment.

MicroRNA-4465 suppresses tumor proliferation and metastasis in non-small cell lung cancer by directly targeting the oncogene EZH2.

MicroRNA-26 (miR-26) has been reported to be connected with tumor progression. MicroRNA-4465 (miR-4465) was one member of miR-26 family, however, the role of miR-4465 in non-small cell lung cancer (NSCLC) was unknown. This study was aimed to explore the function of miR-4465 and investigate whether miR-4465 can be a potential target for treating human NSCLC. QRT-PCR was applied to evaluate the miR-4465 expression levels in NSCLC cells. Then, we demonstrated the role of miR-4465 in NSCLC cells biological characteristics through detecting proliferation, migration and invasion. Luciferase reporter assay and TargetScan were applied to explore the potential target gene of miR-4465. In this study, we found that the miR-4465 expression levels in NSCLC cell lines were significantly reduced when compared to the normal human bronchial epithelial cell lines. And, over expression of miR-4465 could restrain the proliferation, migration and invasion of NSCLC. Moreover, MiR-4465 reduced EZH2 protein expression through the binding sites in 3' -UTR of the EZH2 mRNA, indicating EZH2 may be a direct target gene of miR-4465. Conclusively, miR-4465 suppressed cancer cells proliferation and metastasis by directly targeting the oncogene EZH2 and it may serve as a new potential therapeutic target in NSCLC.

Co-expression network analysis of long noncoding RNAs (IncRNAs) and cancer genes revealsSFTA1P and CASC2abnormalities in lung squamous cell carcinoma.

Lung squamous cell carcinoma(LSCC) is the most common and aggressive lung tumor with poor clinical outcome. Previously studies showed that deregulation of long noncoding RNAs (lncRNAs) were involved in LSCC. We intended to figure out the role of lncRNAs in the regulation process of cancer-related genes and pathways they are involved. Data of 552 samples, including 501 cancer samples and 51 normal ones, were extracted from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DEIs) were screened out (FDR<0.05, |logFC|>1) and then followed by GO ontology and KEGG annotation analysis. Oncogenes from COSMIC data set and Tumor suppressor genes (TSGs) from TSGene data set were collected and analyzed by gene Set Enrichment Analysis (GSEA) . The differentially expressed oncogenes and tumor supressor gene (TSGs) were obtained and co-expression analysis was conducted to generate co-expression lncRNA-gene pairs, which can be helpful in figuring out the role of lncRNA in the regulation of oncogenes and tumor suppressor genes. A total of 31 lncRNAs with low expression levels and 37 lncRNAs with high expression levels were screened out and most of them were enriched in pathways such as meiosis, male gamete generation, defensins. Of note, SFTA1P and CASC2 were found to be related with most of the oncogenes and TSGs by co-expression analysis. We suggested SFTA1P and CASC2 played important role in the regulation of both oncogene and TSGs during the carcinogenesis of LSCC and have the potential to be applied in future diagnosis, prognostic process and target therapy of LSCC.

Three Circulating LncRNA Predict Early Progress of Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Previous studies revealed that circulating (either from plasma or serum) long non-coding RNA may predict the occurrence or prognosis of multiple human malignant tumors. In this study, we mainly explored whether circulating lncRNAs can be utilized as biomarkers predicting the development of human esophageal squamous cell carcinoma (ESCC). METHODS: LncRNA microarray was applied to screen the potential biomarkers for ESCC. Each group contained three individual plasma samples. A multi-stage validation and risk score formula detection were used for validation. RESULTS: Eleven dysregulated lncRNAs were obtained after Venny analysis. Further validation in a larger cohort including 205 ESCC patients, 82 patients suffering from esophagus dysplasia and 210 healthy controls confirmed that increased Linc00152, CFLAR-AS1 and POU3F3 might be potential biomarkers for predicting the early progress with an area under curve (AUC) of 0.698, 0.651 and 0.584, respectively. The merged AUC of the three factors and merged with CEA was 0.765 and 0.955, respectively. We also revealed that circulating levels of three lncRNAs were associated with poor post-surgery prognosis of ESCC patients. CONCLUSIONS: The three circulating lncRNAs might serve as potential biomarkers for predicting the early occurrence of ESCC.