• Anemia
• Lymphocytes
• Metabolomics
• Saponins
• Traditional Chinese medicine

• Animals
• Cyclophosphamide/toxicity
• Panax notoginseng/chemistry
• Mice, Inbred BALB C
• Mice
• Saponins/pharmacology
• Anemia/chemically induced
• Anemia/drug therapy
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/chemistry
• Male
• Cell Line, Tumor
• Female

• KIAA0101
• MA5
• Ovarian cancer
• Yes-associated protein
• glycolysis

Gastrointestinal (GI) cancers, including malignancies in the gastrointestinal tract and accessory organs of digestion, represent the leading cause of death worldwide due to the poor prognosis of most GI cancers. An investigation into the potential molecular targets of prediction, diagnosis, prognosis, and therapy in GI cancers is urgently required. Proliferating cell nuclear antigen (PCNA) clamp associated factor (PCLAF), which plays an essential role in cell proliferation, apoptosis, and cell cycle regulation by binding to PCNA, is a potential molecular target of GI cancers as it contributes to a series of malignant properties, including tumorigenesis, epithelial-mesenchymal transition, migration, and invasion. Furthermore, PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer. In addition to GI cancers, PCLAF is also involved in other types of cancers and autoimmune diseases. Several pivotal pathways, including the Rb/E2F pathway, NF-κB pathway, and p53-p21 cascade, are implicated in PCLAF-mediated diseases. PCLAF also contributes to some diseases through dysregulation of the p53 pathway, WNT signal pathway, MEK/ERK pathway, and PI3K/AKT/mTOR signal cascade. This review mainly describes in detail the role of PCLAF in physiological status and GI cancers. The signaling pathways involved in PCLAF are also summarized. Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

• Proliferating cell nuclear antigen
• Proliferating cell nuclear antigen clamp associated factor
• Transcript variant
• Gastrointestinal cancers
• Signal pathway
• Biological therapeutic

Accumulating evidence indicates that circular (circ)RNAs exhibit complex functions in diverse malignant tumors, including non-small cell lung cancer (NSCLC). The role of the circRNA transcription adaptor 2A (circTADA2A) in NSCLC remains unclear. The expression, function and mechanism of circTADA2A in NSCLC development were investigated in the present study. The results revealed that circTADA2A was upregulated in NSCLC, and that knockdown of circTADA2A inhibited cell proliferation and migration in the NSCLC cell lines A549 and H1299. Functional assays demonstrated that circTADA2A promoted proliferation and migration via interacting with microRNA (miR)-638. Bioinformatics and reverse transcription-quantitative PCR assay confirmed that miR-638 was expressed at low levels in NSCLC. In addition, it was found that miR-638 served a tumor-suppressive role and suppressed proliferation and migration via PCNA clamp associated factor (KIAA0101) inhibition in A549 and H1299 cells. Lastly, it was verified that circTADA2A promoted cell proliferation and migration, at least partially, via miR-638/KIAA0101 signaling in A549 and H1299 cells. In summary, the present study showed that circTADA2A promoted NSCLC cell proliferation and migration via modulating miR-638/KIAA0101 signaling.

• PCNA clamp associated factor
• circular RNA transcription adaptor 2A
• microRNA‑638
• migration
• non‑small cell lung cancer
• proliferation

• Kiaa0101
• biomarker
• invasion
• p38MAPK
• prognosis

• retinoblastoma
• gene expression
• dna methylation
• micrornas
• long noncoding rna
• epigenomics
• computational biology

• Biomarkers, Tumor/genetics
• Computational Biology/methods
• DNA Methylation
• Data Mining
• Databases, Genetic
• Epigenomics
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• Infant
• Infant, Newborn
• Protein Interaction Maps/genetics
• RNA, Long Noncoding/genetics
• RNA, Messenger/genetics
• Retinal Neoplasms/genetics
• Retinoblastoma/genetics

• Cancer heterogeneity
• liquid biopsy
• multi-omics
• proteomics
• renal cell carcinoma

• DNA replication
• ELK1
• KIAA0101
• bioinformatics
• nasopharyngeal carcinoma
• proliferation

Chronic obstructive pulmonary disease (COPD) and squamous cell lung carcinoma (SCC) are smoking-related diseases. However, the connection between the two is poorly understood. Microarray gene expression profiles in bronchial epithelium from patients with SCC with or without COPD were downloaded from the Gene Expression Omnibus repository. Differentially expressed genes associated with COPD and SCC were identified and visualized using the Advanced Network Merger module in Cytoscape. COPD-associated genes in SCC progression were further identified using the BisoGenet plug-in in Cytoscape. The genetic interaction network was predicted using the Network Analysis function. Heat shock protein 90 α family class A member 1 (HSP90AA1), adrenoceptor β2 (ADRB2), transducin β like 1 X-linked receptor 1 (TBL1XR1) and heat shock protein family B (small) member 1 (HSPB1) were identified to be differentially expressed in SCC and COPD cases. The overall survival rate associated with the gene signatures was investigated using clinical samples from patients with SCC and COPD from the PROGgene database. The results suggest that the pathogenesis of SCC caused by COPD is regulated by HSP90AA1, ADRB2, TBL1XR1 and HSPB1. These genes may serve as potential therapeutic targets for the treatment of patients with COPD-related SCC.

• chronic obstructive pulmonary disease
• interaction network
• squamous cell lung carcinoma

• Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis
• bioinformatics analysis
• differentially expressed genes
• lung cancer
• protein-protein interaction
• survival analysis

Spontaneous canine (Canis lupus) oligodendroglioma (ODG) holds tremendous potential as an immunocompetent large animal model of human malignant gliomas (MG). However, the feasibility of utilizing this model in pre-clinical studies depends on a thorough understanding of the similarities and differences of the molecular pathways associated with gliomas between the two species. We have previously shown that canine ODG has an immune landscape and expression pattern of commonly described oncogenes similar to that of human MG. In the current study, we performed a comprehensive analysis of canine ODG RNAseq data from 4 dogs with ODG and 2 normal controls to identify highly dysregulated genes in canine tumors. We then evaluated the expression of these genes in human MG using Xena Browser, a publicly available database. STRING-database inquiry was used in order to determine the suggested protein associations of these differentially expressed genes as well as the dysregulated pathways commonly enriched by the protein products of these genes in both canine ODG and human MG. Our results revealed that 3,712 (23%) of the 15,895 differentially expressed genes demonstrated significant up- or downregulation (log2-fold change > 2.0). Of the 3,712 altered genes, ~50% were upregulated (n = 1858) and ~50% were downregulated (n = 1854). Most of these genes were also found to have altered expression in human MG. Protein association and pathway analysis revealed common pathways enriched by members of the up- and downregulated gene categories in both species. In summary, we demonstrate that a similar pattern of gene dysregulation characterizes both human MG and canine ODG and provide additional support for the use of the canine model in order to therapeutically target these common genes. The results of such therapeutic targeting in the canine model can serve to more accurately predict the efficacy of anti-glioma therapies in human patients.

• anaplastic oligodendroglioma
• canine glioma
• glioblastoma
• malignant glioma
• molecular therapeutic targets

Prostate cancer (PCa) remains a principal issue to be addressed in male cancer-associated mortality. Therefore, the present study aimed to examine the clinical value and associated molecular mechanism of microRNA (miR)-1 in PCa. A meta-analysis was conducted to evaluate the diagnosis of miR-1 in PCa via Gene Expression Omnibus and ArrayExpress datasets, The Cancer Genome Atlas miR-1 expression data and published literature. It was identified that expression of miR-1 was significantly downregulated in PCa. Decreased miR-1 expression possessed moderate diagnostic value, with area under the curve, sensitivity, specificity and odds ratio values at 0.73, 0.77, 0.57 and 4.60, respectively. Using bioinformatics methods, it was revealed that a number of pathways, including the ‘androgen receptor signaling pathway’, ‘androgen receptor activity’, ‘transcription factor binding’ and ‘protein processing in the endoplasmic reticulum’, were important in PCa. A total of seven hub genes, including phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccin ocarboxamide synthase (PAICS), cadherin 1 (CDH1), SRC proto-oncogene, non-receptor tyrosine kinase, twist family bHLH transcription factor 1 (TWIST1), ZW10 interacting kinetochore protein (ZWINT), PCNA clamp associated factor (KIAA0101) and androgen receptor, among which, five (PAICS, CDH1, TWIST1, ZWINT and KIAA0101) were significantly upregulated and negatively correlated with miR-1, were identified as key miR-1 target genes in PCa. Additionally, it was investigated whether miR-1 and its hub genes were associated with clinical features, including age, tumor status, residual tumor, lymph node metastasis, pathological T stage and prostate specific antigen level. Collectively the results suggest that miR-1 may be involved in the progression of PCa, and consequently be a promising diagnostic marker. The ‘androgen receptor signaling pathway’, ‘androgen receptor activity’, ‘transcription factor binding’ and ‘protein processing in the endoplasmic reticulum’ may be crucial interactive pathways in PCa. Furthermore, PAICS, CDH1, TWIST1, ZWINT and KIAA0101 may serve as crucial miR-1 target genes in PCa.

• bone metastasis
• breast cancer
• enrichment analysis
• interaction network
• microarray

• Bone Neoplasms/genetics
• Bone Neoplasms/secondary
• Breast Neoplasms/pathology
• Computational Biology
• Databases, Genetic
• Epistasis, Genetic
• Female
• Humans
• Protein Interaction Maps
• Signal Transduction/genetics
• Transcriptome

Identify genes probably associated with chronic heart failure and predict potential target genes for dilated cardiomyopathy using bioinformatics analyses.

Gene expression profiles (series number GSE3585 and GSE42955) of cardiomyopathy patients and healthy controls were downloaded from the Expression Omnibus Gene (GEO) database. Differential expression of genes (DEGS) between the two groups of total 14 cardiomyopathy patients and 10 healthy controls were subsequently identified by limma package of R. Database for Annotation, Visualization, and Integrated Discovery (DAVID Tool), which is an analysis of enriched biological processes. Search Tool for the Retrieval Interacting Genes (STRING) was used as well for the analysis of protein-protein interaction network (PPI). Prediction of the potential drugs was suggested based on the preliminarily identified genes using Connectivity Map (CMap).

Eighty-nine DEGs were identified (57 up-regulated and 32 down-regulated). The most enrichment Gene Ontology (GO) terms (P < 0.05) contain genes involved in extracellular matrix (ECM) and biological adhesion signal pathways (P < 0.05, ES > 1.5) such as ECM-receptors, focal adhesion and transforming growth factor beta (TGF-β), etc. Fifty-one differentially expressed genes were found to encode interacting proteins. Eleven key genes along with related transcription factors were identified including CTGF, POSTN, CORIN, FIGF, etc.

Bioinformatics-based analyses reveal the targeted genes probably associated with cardiomyopathy, which provide clues for pharmacological therapies aiming at the targets.

• Bioinformatics
• Dilated cardiomyopathy
• Heart failure
• Microarray

Recent studies revealed that some passenger strands of miRNAs acted as anti-tumor or oncogenic miRNAs in cancer cells. In this study, we focused on miR-455-5p (the passenger strand) and miR-455-3p (the guide strand) based on microRNA (miRNA) expression signatures of cancer cells. Both miR-455-5p and miR-455-3p were downregulated in renal cell carcinoma (RCC) tissues and low expression of these miRNAs was significantly associated with poor prognosis. Cancer cell proliferation, migration and invasive abilities were significantly inhibited by ectopic expression of miR-455-5p and miR-455-3p. To identify their oncogenic targets, we applied a combination of genome-wide gene expression and in silico miRNA database analyses. We focused on spindle and kinetochore-associated proteins, SKA1 and SKA3 and demonstrated direct regulation of SKA1 by miR-455-5p and SKA3 by miR-455-3p in RCC cells. Our present data demonstrated overexpression of SKA3 in RCC clinical specimens. Moreover, the study showed that the miR-455-3p/SKA3 axis contributed to cancer cell aggressiveness. Analytic strategies based on anti-tumor miRNAs, including passenger strands of miRNAs, are effective approaches for the elucidation of the molecular pathogenesis of RCC.

• SKA
• anti-tumor
• miR-455
• microRNA
• renal cell carcinoma

• KIAA0101 transcript variant 2
• alternative splicing
• hepatocellular carcinoma
• isoform-selective competitor
• therapeutic drug

Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis. Based on these comprehensive effects, NDGA effectively suppresses tumor metastasis in nude mice model. Our findings reveal a novel mechanism underlying the anti-metastasis function of NDGA and indicate the potential value of NDGA in NRP1 targeting therapy for selected subtypes of cancer.

• cancer cell migration and metastasis
• neuropilin 1
• nordihydroguaiaretic acid
• prostate cancer
• proteomics

In this study, we investigated the molecular pathways regulating breast cancer liver metastasis. We identified 48 differentially expressed genes (4 upregulated and 44 downregulated) by analyzing microarray dataset GSE62598 from Gene Expression Omnibus (GEO). We constructed a genetic interaction network with 84 nodes and 237 edges using the String consortium database. The network was reliably robust with a clustering coefficient (cc) of 0.598 and protein-protein interaction (PPI) enrichment p value of zero. Using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, we identified MAPK, NFκB and VEGF signaling pathways as the most critical pathways regulating breast cancer liver metastasis. These results indicate that the distinct breast cancer metastatic stages, including dissemination from the primary breast tumor, transit through the vasculature, and survival and proliferation in the liver, are regulated by the MAPK, NFκB, and VEGF signaling pathways.

• breast cancer
• interaction network
• liver
• metastasis
• microarray

• differentially expressed genes
• lncrnas
• oral lichen planus
• oral squamous cell carcinoma

• Biomarkers, Tumor/metabolism
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Gene Ontology
• Genome-Wide Association Study
• High-Throughput Nucleotide Sequencing
• Humans
• Lichen Planus, Oral/genetics
• Lichen Planus, Oral/metabolism
• Mouth Mucosa/metabolism
• Mouth Neoplasms/genetics
• Mouth Neoplasms/metabolism
• RNA, Long Noncoding/metabolism
• RNA, Messenger/metabolism

• circulating
• disease activity
• mir-146a
• rheumatoid arthritis
• tripterygium wilfordii hook f

• Antirheumatic Agents/therapeutic use
• Area Under Curve
• Arthritis, Rheumatoid/blood
• Arthritis, Rheumatoid/drug therapy
• Biomarkers/blood
• Drugs, Chinese Herbal/therapeutic use
• Female
• Humans
• Leukocytes, Mononuclear/metabolism
• Male
• MicroRNAs/blood
• Middle Aged
• Phytotherapy
• Prognosis
• ROC Curve
• Risk
• Severity of Illness Index
• Treatment Outcome
• Tripterygium

Carfilzomib is a Food and Drug Administration-approved selective proteasome inhibitor for patients with multiple myeloma (MM). However, recent studies indicate that MM cells still develop resistance to carfilzomib, and the molecular mechanisms associated with carfilzomib resistance have not been studied in detail. In this study, to better understand its potential resistant effect and its underlying mechanisms in MM, microarray gene expression profile associated with carfilzomib-resistant KMS-11 and its parental cell line was downloaded from Gene Expression Omnibus database. Raw fluorescent signals were normalized and differently expressed genes were identified using Significance Analysis of Microarrays method. Genetic interaction network was expanded using String, a biomolecular interaction network JAVA platform. Meanwhile, molecular function, biological process and signaling pathway enrichment analysis were performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Totally, 27 upregulated and 36 downregulated genes were identified and a genetic interaction network associated with the resistant effect was expanded basing on String, which consisted of 100 nodes and 249 edges. In addition, signaling pathway enrichment analysis indicated that cytokine–cytokine receptor interaction, autophagy, ErbB signaling pathway, microRNAs in cancer and fatty acid metabolism pathways were aberrant in carfilzomib-resistant KMS-11 cells. Thus, in this study, we demonstrated that carfilzomib potentially conferred drug resistance to KMS-11 cells by cytokine–cytokine receptor interaction, autophagy, ErbB signaling pathway, microRNAs in cancer and fatty acid metabolism pathways, which may provide some potential molecular therapeutic targets for drug combination therapy against carfilzomib resistance.

• carfilzomib
• compensate pathways
• drug resistance
• interaction network
• microarray
• multiple myeloma

• Renal cell carcinoma
• biological fluids
• biomarkers
• cancer
• kidney
• mass spectrometry imaging
• peptidome
• proteome
• proteomics
• tissue

• RUV-inv
• endometrium
• gene array
• inflammation
• menstruation
• repair