Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer

The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE33482","term_id":"33482"}}GSE33482, {"type":"entrez-geo","attrs":{"text":"GSE28646","term_id":"28646"}}GSE28646, and {"type":"entrez-geo","attrs":{"text":"GSE15372","term_id":"15372"}}GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), and then their associations with drug resistance was analyzed by comprehensive bioinformatic analyses. Nine microRNAs (microRNA-199a-5p, microRNA-199a-3p, microRNA-199b-3p, microRNA-215, microRNA-335, microRNA-18b, microRNA-363, microRNA-645 and microRNA-141) and 38 genes were identified to be differentially expressed in drug-resistant ovarian cancer cells, with seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA and PI15) exhibited exactly the same expression trends in all three microarrays. Biological process annotation and pathway enrichment analysis of the 9 microRNAs and 38 genes identified several drug resistant-related signaling pathways, and the microRNA-mRNA interaction revealed the existence of a targeted regulatory relationship between the 9 microRNAs and most of the 38 genes. The expression of 9 microRNAs and the 7 genes by qRT-PCR in SKOV3/DDP and A2780/DDP cells indicating a consistent expression profile with the microarrays. Among those, the expression of EPHA7 and PI15 were negatively correlated with that of microRNA-141, and they were also identified as potential targets of this microRNA via microRNA-mRNA interaction. We thus concluded that microRNA-141, EPHA7, and PI15 might jointly participate in the regulation of drug resistance in ovarian cancer and serve as potential targets in targeted therapies.     

Identification of collaboration patterns of dysfunctional pathways in breast cancer

Breast cancer (BC) is the most common malignancy among women. We aimed to illuminate the molecular dysfunctional mechanisms of BC progression. The mRNA expression profile of BC {"type":"entrez-geo","attrs":{"text":"GSE15852","term_id":"15852"}}GSE15852 was downloaded from Gene Expression Omnibus database, including 43 normal samples and 43 cancer samples. Differentially expressed genes (DEGs) in BC were screened using the t-test by Benjamin and Hochberg method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the selected DEGs were enriched using Hypergeomeric distribution model. In addition, functional similarity network among the enriched pathways was constructed to further analyze the collaboration of these pathways. We found 848 down-regulated DEGs were associated with 16 significant dysfunctional pathways, including PPAR signaling fatty acid metabolism, and 1584 up-regulated DEGs were related to 6 significant dysfunctional pathways, like cell cycle, protein export, and antigen processing and presentation in BC samples. Crosstalk network analysis of pathways indicated that pyruvate metabolism, propanoate metabolism, and glycolysis gluconeogenesis were the pathways with closest connections with other pathways in BC. In addition, other antigen processing and presentation, including 19 DEGs; PPAR signaling pathway, including 18 DEGs; and pyruvate metabolism pathway, including 13 DEGs were further analyzed. Our results suggested that dysfunctional of significant pathways can greatly affect the progression of BC. Several significant disorder pathways were enriched in our comprehensive study. They may provide guidelines to explore the dysfunctional mechanism of BC progression.     

Identification of Key Genes and Pathways associated with Endometriosis by Weighted Gene Co-expression Network Analysis

Background: Endometriosis is a common gynecological disorder with high rates of infertility and pelvic pain. However, its pathogenesis and diagnostic biomarkers remain unclear. This study aimed to elucidate potential hub genes and key pathways associated with endometriosis in ectopic endometrium (EC) and eutopic endometrium (EU).Material and Method: EC and EU-associated microarray datasets were obtained from the gene expression omnibus (GEO) database. Gene set enrichment analysis was performed to obtain further biological insight into the EU and EC-associated genes. Weighted gene co-expression network analysis (WGCNA) was performed to find clinically significant modules of highly-correlated genes. The hub genes that belong to both the weighted gene co-expression network and protein-protein interaction (PPI) network were identified using a Venn diagram.Results: We obtained EC and EU-associated microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE7305","term_id":"7305"}}GSE7305 and {"type":"entrez-geo","attrs":{"text":"GSE120103","term_id":"120103"}}GSE120103. Genes in the EC were mainly enriched in the immune response and immune cell trafficking, and genes in the EU were mainly enriched in stress response and steroid hormone biosynthesis. PPI networks and weighted gene co-expression networks were constructed. An EC-associated blue module and an EU-associated magenta module were identified, and their function annotations revealed that hormone receptor signaling or inflammatory microenvironments may promote EU passing through the oviducts and migrating to the ovarian surfaces, and adhesion and immune correlated genes may induce the successful ectopic implantation of the endometrium (EC). Twelve hub genes in the EC and sixteen hub genes in the EU were recognized and further validated in independent datasets.Conclusion: Our study identified, for the first time, the hub genes and enrichment pathways in the EC and EU using WGCNA, which may provide a comprehensive understanding of the pathogenesis of endometriosis and have important clinical implications for the treatment and diagnosis of endometriosis.     

Interaction of key pathways in sorafenib-treated hepatocellular carcinoma based on a PCR-array

This study aimed to identify the key pathways and to explore the mechanism of sorafenib in inhibiting hepatocellular carcinoma (HCC). The gene expression profile of {"type":"entrez-geo","attrs":{"text":"GSE33621","term_id":"33621"}}GSE33621, including 6 sorafenib treated group and 6 control samples, was downloaded from the GEO (Gene Expression Omnibus) database. The differentially expressed genes (DEGs) in HCC samples were screened using the ΔΔCt method with the homogenized internal GAPDH. Also, the functions and pathways of DEGs were analyzed using the DAVID. Moreover, the significant pathways of DEGs that involved in HCC were analyzed based on the Latent pathway identification analysis (LPIA). A total of 44 down-regulated DEGs were selected in HCC samples. Also, there were 84 biological pathways that these 44 DEGs involved in. Also, LPIA showed that Osteoclast differentiation and hsa04664-Fc epsilon RI signaling pathway was the most significant interaction pathways. Moreover, Apoptosis, Toll-like receptor signaling pathway, Chagas disease, and T cell receptor signaling pathway were the significant pathways that interacted with hsa04664. In addition, DEGs such as AKT1 (v-akt murine thymoma viral oncogene homolog 1), TNF (tumor necrosis factor), SYK (spleen tyrosine kinase), and PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1 (alpha)) were the common genes that involved in the significant pathways. Several pathway interaction pairs that caused by several downregulated genes such as SYK, PI3K, AKT1, and TNF, were identified play curial role in sorafenib treated HCC. Sorafenib played important inhibition roles in HCC by affecting a complicate pathway interaction network.     

Integrated regulatory mechanisms of miRNAs and targeted genes involved in colorectal cancer

Purpose: CRC (Colorectal cancer) is a lethal cancer for death worldwide and the underlying pathological mechanisms for CRC progression remain unclear. We aimed to explore the regulatory mechanism of CRC and provide novel biomarkers for CRC screening. Methods: Downloading from GEO (Gene Expression Omnibus) database, Microarray data {"type":"entrez-geo","attrs":{"text":"GSE44861","term_id":"44861"}}GSE44861 were consisted of 111 colon tissues samples including 55 from adjacent noncancerous tissues and 56 from tumors tissues. After data pre-processing, up- and down regulated DEGs (differentially expressed genes) were identified using Bayes moderated t-test. Then DIVAD (Database for Annotation, Visualization and Integrated Discovery) was recruited to perform functional analysis for DEGs. Thereafter, PPI (protein-protein interaction) network was constructed by mapping DEGs into STRING (Search Tool for the Retrieval of Interacting Genes) database. Further, PPI modules were constructed and the protein domains of DEGs in the modules were analyzed. Moreover, miRNA regulatory network was established through GSEA (gene set enrichment analysis) method. Results: In summary, 96 up- and 212 down-regulated DEGs were identified. Totally, ten DEGs with high degrees in the constructed PPI network were selected, in which COLL1A1, PTGS2 and ASPN were also identified as crucial genes in PPI modules. Furthermore, COLL1A1 was predicted to be targeted by miR-29, while PTGS2 and ASPN were both predicted to be regulated by miR-101 and miR-26. Conclusion: COL11A1 might involve in the progression of CRC via being targeted by miR-29, whereas PTGS2 and ASPN were both regulated by miR-101 and miR-26. Moreover, ASPN may be supposed as a novel biomarker for CRC detection and prevention.     

Differences in gene expression profiles and signaling pathways in rhabdomyolysis-induced acute kidney injury

Purpose: Rhabdomyolysis is a threatening syndrome because it causes the breakdown of skeletal muscle. Muscle destruction leads to the release of myoglobin, intracellular proteins, and electrolytes into the circulation. The aim of this study was to investigate the differences in gene expression profiles and signaling pathways upon rhabdomyolysis-induced acute kidney injury (AKI). Methods: In this study, we used glycerol-induced renal injury as a model of rhabdomyolysis-induced AKI. We analyzed data and relevant information from the Gene Expression Omnibus database (No: {"type":"entrez-geo","attrs":{"text":"GSE44925","term_id":"44925"}}GSE44925). The gene expression data for three untreated mice were compared to data for five mice with rhabdomyolysis-induced AKI. The expression profiling of the three untreated mice and the five rhabdomyolysis-induced AKI mice was performed using microarray analysis. We examined the levels of Cyp3a13, Rela, Aldh7a1, Jun, CD14. And Cdkn1a using RT-PCR to determine the accuracy of the microarray results. Results: The microarray analysis showed that there were 1050 downregulated and 659 upregulated genes in the rhabdomyolysis-induced AKI mice compared to the control group. The interactions of all differentially expressed genes in the Signal-Net were analyzed. Cyp3a13 and Rela had the most interactions with other genes. The data showed that Rela and Aldh7a1 were the key nodes and had important positions in the Signal-Net. The genes Jun, CD14, and Cdkn1a were also significantly upregulated. The pathway analysis classified the differentially expressed genes into 71 downregulated and 48 upregulated pathways including the PI3K/Akt, MAPK, and NF-κB signaling pathways. Conclusion: The results of this study indicate that the NF-κB, MAPK, PI3K/Akt, and apoptotic pathways are regulated in rhabdomyolysis-induced AKI.     

Dysregulation of KIF14 regulates the cell cycle and predicts poor prognosis in cervical cancer: a study based on integrated approaches

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The {"type":"entrez-geo","attrs":{"text":"GSE63514","term_id":"63514"}}GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.     

Gene expression profiling analysis of lung adenocarcinoma

The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The {"type":"entrez-geo","attrs":{"text":"GSE2514","term_id":"2514"}}GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma.     

A novel lncRNA-mRNA-miRNA signature predicts recurrence and disease-free survival in cervical cancer

Cervical cancer (CC) patients have a poor prognosis due to the high recurrence rate. However, there are still no effective molecular signatures to predict the recurrence and survival rates for CC patients. Here, we aimed to identify a novel signature based on three types of RNAs [messenger RNA (mRNAs), microRNA (miRNAs), and long non-coding RNAs (lncRNAs)]. A total of 763 differentially expressed mRNAs (DEMs), 46 lncRNAs (DELs), and 22 miRNAs (DEMis) were identified between recurrent and non-recurrent CC patients using the datasets collected from the Gene Expression Omnibus ({"type":"entrez-geo","attrs":{"text":"GSE44001","term_id":"44001"}}GSE44001; training) and The Cancer Genome Atlas (RNA- and miRNA-sequencing; testing) databases. A competing endogenous RNA network was constructed based on 23 DELs, 15 DEMis, and 426 DEMs, in which 15 DELs, 13 DEMis, and 390 DEMs were significantly associated with disease-free survival (DFS). A prognostic signature, containing two DELs (CD27-AS1, LINC00683), three DEMis (hsa-miR-146b, hsa-miR-1238, hsa-miR-4648), and seven DEMs (ARMC7, ATRX, FBLN5, GHR, MYLIP, OXCT1, RAB39A), was developed after LASSO analysis. The built risk score could effectively separate the recurrence rate and DFS of patients in the high- and low-risk groups. The accuracy of this risk score model for DFS prediction was better than that of the FIGO (International Federation of Gynecology and Obstetrics) staging (the area under receiver operating characteristic curve: training, 0.954 vs 0.501; testing, 0.882 vs 0.656; and C-index: training, 0.855 vs 0.539; testing, 0.711 vs 0.508). In conclusion, the high predictive accuracy of our signature for DFS indicated its potential clinical application value for CC patients.     

Construction of ceRNA network and identification of two differentially expressed circRNAs in hepatocellular carcinoma by bioinformatic analysis

Covalently closed circular RNAs (circRNAs) display dysregulated expression in several types of cancer. However, their functions remain largely unclear. In this work, datasets {"type":"entrez-geo","attrs":{"text":"GSE125469","term_id":"125469"}}GSE125469 and {"type":"entrez-geo","attrs":{"text":"GSE128274","term_id":"128274"}}GSE128274 of hepatocellular carcinoma (HCC) were selected from Gene Expression Omnibus (GEO) database. To identify differentially expressed genes (DEGs) in HCC and adjacent tissues, we used R package DESeq for analysis. Then, 15 DEcircRNAs, 65 DEmiRNAs, and 2084 DEmRNAs were identified comparing HCC and normal tissues. Next, to predict the target relationship of circRNA-miRNA and miRNA-mRNA in DEGs, we use the databases CircInteractome and starBase v2.0 for analysis. Finally, the ceRNA network of circRNA-miRNA-mRNA was established by Cytoscape software based on 2 DEcircRNAs (hsa_circ_0007813 and hsa_circ_0089372), 2 DEmiRNAs, and 98 DEmRNAs. In addition, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs to explore the function of DEGs in HCC. Functional enrichment analyses indicated DEmRNAs might be associated with HCC occurrence and progression. In general, our research reveals an important role of ceRNA’s molecular mechanism in HCC.     

BC047440 antisense eukaryotic expression vectors inhibited HepG2 cell proliferation and suppressed xenograft tumorigenicity

The biological functions of the {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 gene highly expressed by hepatocellular carcinoma (HCC) are unknown. The objective of this study was to reconstruct antisense eukaryotic expression vectors of the gene for inhibiting HepG₂ cell proliferation and suppressing their xenograft tumorigenicity. The full-length {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 cDNA was cloned from human primary HCC by RT-PCR. {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 gene fragments were ligated with pMD18-T simple vectors and subsequent pcDNA3.1(+) plasmids to construct the recombinant antisense eukaryotic vector pcDNA3.1(+)BC047440AS. The endogenous {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 mRNA abundance in target gene-transfected, vector-transfected and naive HepG₂ cells was semiquantitatively analyzed by RT-PCR and cell proliferation was measured by the MTT assay. Cell cycle distribution and apoptosis were profiled by flow cytometry. The in vivo xenograft experiment was performed on nude mice to examine the effects of antisense vector on tumorigenicity. {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 cDNA fragments were reversely inserted into pcDNA3.1(+) plasmids. The antisense vector significantly reduced the endogenous {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 mRNA abundance by 41% in HepG₂ cells and inhibited their proliferation in vitro (P < 0.01). More cells were arrested by the antisense vector at the G₁ phase in an apoptosis-independent manner (P = 0.014). Additionally, transfection with pcDNA3.1(+) BC047440AS significantly reduced the xenograft tumorigenicity in nude mice. As a novel cell cycle regulator associated with HCC, the {"type":"entrez-nucleotide","attrs":{"text":"BC047440","term_id":"28703691","term_text":"BC047440"}}BC047440 gene was involved in cell proliferation in vitro and xenograft tumorigenicity in vivo through apoptosis-independent mechanisms.     

Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

Background: MiRNAs are pivotal regulators involved in proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in hepatocellular carcinoma (HCC). The aim of this study was to investigate the influence of miR-139-5p and its target genes on the outcomes of HCC.Methods: Survival analysis of miR-139-5p in HCC was conducted in Kaplan-Meier plotter. Target genes of miR-139-5p were identified in TargetScan, miRTarBase and starBase. Gene Expression Omnibus (GEO) series were used for the validation of miR-139-5p target genes. Cox proportional regression model was also established.Results: In Kaplan-Meier plotter, 163 HCC patients were included. MiR-139-5p downregulation was significantly associated with unfavorable overall survival (OS) and disease-free survival (DFS) in HCC patients (all P < 0.001). MiR-139-5p was significantly downregulated in HCC tumors and human hepatoma cell lines (all P < 0.05). As a target gene of miR-139-5p, CCT5 was overexpressed in HCC tumor tissues and peripheral blood mononuclear cells (all P < 0.05). A negative correlation between CCT5 and miR-139-5p was found in TCGA dataset. CCT5 overexpression was significantly associated with worse OS in HCC patients (P < 0.001), which was validated in the {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 dataset (P = 0.017). CCT5 mRNA was significantly overexpressed in HCC patients with alpha-fetoprotein (AFP) > 300 ng/ml, BCLC staging B-C, TNM staging III and main tumor size > 5 cm (all P < 0.05). According to the Cox regression model of CCT5-interacting genes, HCC patients with high risk had poor OS compared to those with low risk in the TCGA dataset (P < 0.001), with the 1-year, 3-year, and 5-year ROC curves of an area under the curve (AUC) equal to 0.704, 0.662, and 0.631, respectively.Conclusions: MiR-139-5p suppresses HCC tumor aggression and conversely correlated with CCT5. The miR-139-5p/CCT5 axis might perform crucial functions in the development of HCC.     

SN50 enhances the effects of LY294002 on cell death induction in gastric cancer cell line SGC7901

Introduction

In the previous study, we found that the inhibition of phosphatidylinositol 3-kinase (PI3K) by {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 induced SGC7901 cell death in vitro. We did not know whether SN50, which is a specific inhibitor of nuclear factor κB (NF-κB), could increase the cell death induction of gastric cancer of {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 in vitro, and we also wanted to know the mechanism of it, which might be applied to clinical tumor therapy.

Material and methods

The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxic effects of the drugs. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Hoechst 33258 staining was used to detect apoptosis and necrosis morphological changes after {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and/or SN50 treatment. Expression of p53, PUMA and Beclin1 were determined with real-time polymerase chain reaction (RT-PCR) analysis. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and/or SN50 treatment.

Results

In this study, we found that treating the human gastric cancer cells SGC7901 with SN50 could significantly enhance the effects of {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 on inducing cell death after 24 h, compared to the control group (p < 0.05). Detection of mitochondrial potential and transmission electron microscopic examination indicated that the rate of cell death increased progressively. The expression of p53, PUMA and Beclin1 was up-regulated.

Conclusions

The NF-κB inhibitor SN50 could enhance the role of {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 on inducing cell death of human gastric cancer cells SGC7901, which might be a promising new approach to gastric cancer therapy.     

Upregulation of Heat Shock Proteins (HSPA12A,HSP90B1, HSPA4, HSPA5 and HSPA6) in Tumour Tissues Is Associated with Poor Outcomes from HBV-Related Early-Stage Hepatocellular Carcinoma

Background: Heat shock proteins (HSPs) are overexpressed in human hepatocellular carcinoma (HCC) tissue and correlate with aggressiveness and prognosis of HCC.Methods: Using the {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 microarray expression profile from Gene Expression Omnibus, we compared HSP gene expression between tumour and non-tumour tissues and correlated this with outcomes in HCC patients.Results: We analysed 220 hepatitis B virus (HBV)-related HCC patients and 25 HSPs in this study. With the exception of HSPA4L, HSPA12A and HSPB8, members of the HSP family, including HSPH1, HSPBP1, HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA5, HSPA8, HSPA9, HSPAA1, HSPAB1, HSPA14, HSPB11, HSPA13, HSP90B1 and HSPBAP1, were all overexpressed in tumour tissues (all P < 0.001). In contrast, HSPB6, HSPB7, HSPA6, HSPB2 and HSPB3 were upregulated in non-tumour tissues (all P < 0.001). Multivariate analysis showed that cirrhosis (HR = 5.282, 95% CI = 1.294-21.555, P = 0.02), Barcelona Clinic liver cancer (BCLC) staging (HR = 2.151, 95% CI = 1.682-2.750, P < 0.001), HSPA12A (HR = 1.042, 95% CI = 1.003-1.082, P = 0.033) and HSP90B1 (HR = 1.001, 95% CI = 1.000-1.001, P = 0.011) were negatively associated with survival of HBV-related HCC patients. Furthermore, advanced BCLC staging (HR = 1.797, 95% CI = 1.439-2.244, P < 0.001) was also associated with earlier recurrence of HCC. The high expression of HSPA4 (HR = 1.002, 95% CI = 1.000-1.004, P = 0.019), HSPA5 (HR = 1.0, 95% CI = 1.0-1.0, P = 0.046) and HSPA6 (HR = 1.008, 95% CI = 1.001-1.015, P = 0.021) was similarly associated with HCC recurrence.Conclusions: The expression of most HSPs was higher in tumour tissues than in non-tumour tissues. High BCLC staging scores, advanced cirrhosis and the overexpression of HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC.     

Differences in key genes in human alveolar macrophages between phenotypically normal smokers and nonsmokers: diagnostic and prognostic value in lung cancer

Objective: To explore the effect of smoking on gene expression in human alveolar macrophages and the value of identified key genes in the early diagnosis and prognosis of lung cancers. Methods: We downloaded three data sets ({"type":"entrez-geo","attrs":{"text":"GSE8823","term_id":"8823"}}GSE8823, {"type":"entrez-geo","attrs":{"text":"GSE2125","term_id":"2125"}}GSE2125, and {"type":"entrez-geo","attrs":{"text":"GSE3212","term_id":"3212"}}GSE3212) from the Gene Expression Omnibus (GEO) database, including 31 non-smoking and 33 smoking human alveolar macrophage samples. We identified common differentially expressed genes (DEGs), from which we obtained module genes and hub genes by using STRING and Cytoscape. Then we analyzed the protein-protein interaction (PPI) network of DEGs, hub genes, and module genes and used David online analysis tool to carry out functional enrichment analysis of DEGs and module genes. Results: A total of 85 differentially expressed genes was obtained, including 42 up-regulated genes and 43 down-regulated genes. The Human Protein Atlas and Survival analysis showed that GBP1, ITGAM, CSF1, SPP1, COL1A1, LAMB1 and THBS1 may be closely associated with the carcinogenesis and prognosis of lung cancer. Conclusion: DEGs, module, and hub genes identified in the present study help explain the effects of smoking on human alveolar macrophages and provide candidate targets for diagnosis and treatment of smoking-related lung cancer.     

Downregulation of NUF2 inhibits tumor growth and induces apoptosis by regulating lncRNA AF339813

Recent studies have shown that NUF2 (Ndc80 kinetochore complex component) play important roles in multiple human cancers. In our previous report, NUF2 expression was stronger in tumor tissues than in normal pancreatic tissues. However, whether and how NUF2 play a role in pancreatic cancer progression remains largely unknown. The aim of our study is to investigate the expression and functional role of NUF2 in human PC. NUF2 expression was measured in 10 pairs of PC cancerous and noncancerous tissue samples by quantitative real-time PCR. The effects of NUF2 on PC cells were studied by RNA interference. Apoptosis and cell cycle were analyzed by flow cytometry. Cells viability was evaluated using MTT. CDK4/CDK6 activity was measured by Western blot assay. LncRNAs regulated by NUF2 were gained from bioinformatics analysis. The role of LncRNA {"type":"entrez-nucleotide","attrs":{"text":"AF339813","term_id":"13507351","term_text":"AF339813"}}AF339813, regulated by NUF2, was finally characterized in PC cells by siRNA. Our results showed that NUF2 mRNA and protein were significantly overexpressed in Human PC tissues and several PC cell lines. Through bioinformatics analysis and knockdown NUF2 in PC cells, we found LncRNA {"type":"entrez-nucleotide","attrs":{"text":"AF339813","term_id":"13507351","term_text":"AF339813"}}AF339813 was positively regulated by NUF2. We further demonstrated that knockdown of {"type":"entrez-nucleotide","attrs":{"text":"AF339813","term_id":"13507351","term_text":"AF339813"}}AF339813 by siRNA in PC cells significantly reduced cell proliferation and promoted apoptosis. Thus, we conclude that NUF2 is consistently overexpressed in human PC and NUF2 is closely linked with human PC progression through the meditator LncRNA {"type":"entrez-nucleotide","attrs":{"text":"AF339813","term_id":"13507351","term_text":"AF339813"}}AF339813. Our studies may contribute to understand the molecular mechanism of PC pathogenesis and clinical therapy.     

Long noncoding RNA AK056155 involved in the development of Loeys-Dietz syndrome through AKT/PI3K signaling pathway

Loeys-Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder, and most of LDS patients will develop into aortic aneurysm. Unfortunately, there is no known cure, and a high risk of death from aortic aneurysm rupture. However the detailed mechanism is still unknown. In order to explore the mechanism, we firstly used bioinformatics to predict, and then verified with biology methods. Firstly, we found that LncRNA {"type":"entrez-nucleotide","attrs":{"text":"AK056155","term_id":"16551480","term_text":"AK056155"}}AK056155 was differentially expressed in peripheral blood circulating endothelial cells between normal patients and LDS patients by bioinformatics. Then we further verified that {"type":"entrez-nucleotide","attrs":{"text":"AK056155","term_id":"16551480","term_text":"AK056155"}}AK056155 was also overexpressed in aortic aneurysm patients by RT-PCR. Moreover, we demonstrated that the expression of {"type":"entrez-nucleotide","attrs":{"text":"AK056155","term_id":"16551480","term_text":"AK056155"}}AK056155 can be enhanced by TGF-β1 in a concentration or time depended manner in HUVECs by RT-PCR. Furthermore, the expression of {"type":"entrez-nucleotide","attrs":{"text":"AK056155","term_id":"16551480","term_text":"AK056155"}}AK056155 was reduced with treatment of PI3K inhibitor ({"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002) or AKT inhibitor (GDC-0068) in combination with TGF-β1. These results indicate that {"type":"entrez-nucleotide","attrs":{"text":"AK056155","term_id":"16551480","term_text":"AK056155"}}AK056155 involved in the development of Loeys-Dietz syndrome through AKT/PI3K signaling pathway, it may provide a promising target gene to prevent LDS develop in to aortic aneurysm.