CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

High expression of centromere protein A and its molecular mechanism and clinical significance in prostate cancer: A study based on data mining and immunohistochemistry.

The progression of prostate cancer (PCa) leads to poor prognosis. However, the molecular mechanism of PCa is still not completely clear. This study aimed to elucidate the important role of centromere protein A (CENPA) in PCa. Large numbers of bulk RNA sequencing (RNA-seq) data and in-house immunohistochemistry data were used in analysing the expression level of CENPA in PCa and metastatic PCa (MPCa). Single-cell RNA-seq data was used to explore the expression status of CENPA in different prostate subpopulations. Enrichment analysis was employed to detect the function of CENPA in PCa. Clinicopathological parameters analysis was utilised in analysing the clinical value of CENPA. The results showed that CENPA was upregulated in PCa (standardised mean difference [SMD] = 0.83, p = 0.001) and MPCa (SMD = 0.61, p = 0.029). CENPA was overexpressed in prostate cancer stem cells (CSCs) with androgen receptor (AR) negative compared to epithelial cells with AR positive. CENPA may influence the development of PCa through affecting cell cycle. Patients with nodal metastasis had higher expression level of CENPA. And patients with high CENPA expression had poor disease-free survival. Taken together, Overexpression of CENPA may influence the development of PCa by regulating cell cycle and promoting metastasis.

Clinical Implication of E2F Transcription Factor 1 in Hepatocellular Carcinoma Tissues.

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains challenging and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

Downregulation of zinc finger protein 71 in laryngeal squamous cell carcinoma tissues and its potential molecular mechanism and clinical significance: a study based on immunohistochemistry staining and data mining.

BACKGROUND: The molecular mechanism of laryngeal squamous cell carcinoma (LSCC) is not completely clear, which leads to poor prognosis and treatment difficulties for LSCC patients. To date, no study has reported the exact expression level of zinc finger protein 71 (ZNF71) and its molecular mechanism in LSCC. METHODS: In-house immunohistochemistry (IHC) staining (33 LSCC samples and 29 non-LSCC samples) was utilized in analyzing the protein expression level of ZNF71 in LSCC. Gene chips and high-throughput sequencing data collected from multiple public resources (313 LSCC samples and 192 non-LSCC samples) were utilized in analyzing the exact mRNA expression level of ZNF71 in LSCC. Single-cell RNA sequencing (scRNA-seq) data was used to explore the expression status of ZNF71 in different LSCC subpopulations. Enrichment analysis of ZNF71, its positively and differentially co-expressed genes (PDCEGs), and its downstream target genes was employed to detect the potential molecular mechanism of ZNF71 in LSCC. Moreover, we conducted correlation analysis between ZNF71 expression and immune infiltration. RESULTS: ZNF71 was downregulated at the protein level (area under the curve [AUC] = 0.93, p < 0.0001) and the mRNA level (AUC = 0.71, p = 0.023) in LSCC tissues. Patients with nodal metastasis had lower protein expression level of ZNF71 than patients without nodal metastasis (p < 0.05), and male LSCC patients had lower mRNA expression level of ZNF71 than female LSCC patients (p < 0.01). ZNF71 was absent in different LSCC subpopulations, including cancer cells, plasma cells, and tumor-infiltrated immune cells, based on scRNA-seq analysis. Enrichment analysis showed that ZNF71 and its PDCEGs may influence the progression of LSCC by regulating downstream target genes of ZNF71. These downstream target genes of ZNF71 were mainly enriched in tight junctions. Moreover, downregulation of ZNF71 may influence the development and even therapy of LSCC by reducing immune infiltration. CONCLUSION: Downregulation of ZNF71 may promote the progression of LSCC by reducing tight junctions and immune infiltration; this requires further study.

Expression of IER3 in hepatocellular carcinoma: clinicopathology, prognosis, and potential regulatory pathways.

Background: Immediate early response 3 (IER3) is correlated to the prognosis of several cancers, but the precise mechanisms underlying the regulation by IER3 of the occurrence and development of hepatocellular carcinoma (HCC) remain unknown. Methods: The expression level of IER3 was examined by using in-house immunohistochemistry (IHC), public gene chip, and public RNA-sequencing (RNA-seq). The standardized mean difference (SMD) was calculated to compare the expression levels of IER3 between HCC patients and controls. The summary receiver operating characteristics (sROC) was plotted to comprehensively understand the discriminatory capability of IER3 between HCC and non-HCC group. The Kaplan-Meier curves and the combined hazard ratios (HRs) were used to determine the prognostic value of IER3 in HCC. Moreover, differentially expressed genes (DEGs) and co-expression genes (CEGs) were used to explored the molecular mechanisms of IER3 underlying HCC. hTFtarget was used to predict the transcription factors (TFs) of IER3. The binding site of TFs and the IER3 promoter region was forecasted using the JASPAR website. The relevant ChIP-seq data were used to determine whether TF peaks were present in the IER3 transcription initiation. Results: A significantly increased expression of IER3 protein was found in HCC tissue relative to non-HCC tissue as detected by IHC (p < 0.001). Compared to 1,263 cases of non-HCC tissues, IER3 in 1483 cases of HCC tissues was upregulated (SMD = 0.42, 95% confidence interval [CI] [0.09-0.76]). The sROC showed that IER3 had a certain ability at differentiating HCC tissues (area under the curve (AUC) = 0.65, 95% CI [0.61-0.69]). Comprehensive analysis of the effect of IER3 on the prognosis of patients with HCC demonstrated that higher IER3 expression was associated with poor prognosis in HCC (HRs = 1.30, 95% CI [1.03-1.64]). Pathway enrichment analysis revealed that IER3-related genes were mostly enriched in the PI3K-Akt signaling pathway, cancer-related signaling pathways, the p53 signaling pathway, and other signaling pathways. Regulatory factor X5 (RFX5) was identified as a possible regulator of IER3-related TF. Conclusion: IER3 may be a potential prognostic marker for HCC. The molecular mechanisms of IER3 in HCC warrant further study.

Identification of hub genes in colon cancer via bioinformatics analysis.

OBJECTIVES: This study aimed to investigate hub genes and their prognostic value in colon cancer via bioinformatics analysis. METHODS: Differentially expressed genes (DEGs) of expression profiles (GSE33113, GSE20916, and GSE37364) obtained from Gene Expression Omnibus (GEO) were identified using the GEO2R tool and Venn diagram software. Function and pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were verified based on The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. RESULTS: We identified 207 DEGs, 62 upregulated and 145 downregulated genes, enriched in Gene Ontology terms "organic anion transport," "extracellular matrix," and "receptor ligand activity", and in the Kyoto Encyclopedia of Genes and Genomes pathway "cytokine-cytokine receptor interaction." The PPI network was constructed and nine hub genes were selected by survival analysis and expression validation. We verified these genes in the TCGA database and selected three potential predictors (ZG16, TIMP1, and BGN) that met the independent predictive criteria. TIMP1 and BGN were upregulated in patients with a high cancer risk, whereas ZG16 was downregulated. The immunostaining results from HPA supported these findings. CONCLUSION: This study indicates that these hub genes may be promising prognostic indicators or therapeutic targets for colon cancer.

Prognostic alternative splicing signature in cervical squamous cell carcinoma.

Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent-splice-in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival-associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein-protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low-risk group had a longer survival period than high-risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy.

Upregulation of miR­132­3p in cholangiocarcinoma tissues: A study based on RT­qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses.

MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR­132­3p and CCA remains unknown. In the present study, the clinical role of miR­132­3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription­quantitative PCR (RT­qPCR), CCA­associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA­microarray or miRNA­sequencing data were screened, and meta­analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR­132­3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA­sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein­protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non­tumor biliary epithelium. The meta­analyses comprised 10 groups of RT­qPCR data, eight GEO microarray datasets and one TCGA miRNA­sequencing dataset. The SMD of miR­132­3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR­132­3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR­132­3p in the early stage of CCA (stages I­II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III­IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR­132­3p level in low­grade CCA (grades G1­G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high­grade CCA (grades G3­G4) (P=0.037). Furthermore, 555 potential target genes of miR­132­3p in CCA were mainly enriched in the 'Focal Adhesion­PI3K­Akt­mTOR­signaling pathway'. In conclusion, upregulation of miR­132­3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.

Construction of a model to predict the prognosis of patients with cholangiocarcinoma using alternative splicing events.

Cholangiocarcinoma (CCA) is a type of malignant tumor that originates in the mucosal epithelial cells of the biliary system. It is a highly aggressive cancer that progresses rapidly, has low surgical resection rates and a high recurrence. At present, no prognostic molecular biomarker for CCA has been identified. However, CCA progression is affected by mRNA precursors that modify gene expression levels and protein structures through alternative splicing (AS) events, which create molecular indicators that may potentially be used to predict CCA outcomes. The present study aimed to construct a model to predict CCA prognosis based on AS events. Using prognostic data available from The Cancer Genome Atlas, including the percent spliced index of AS events obtained from TCGASpliceSeq in 32 CCA cases, univariate and multivariate Cox regression analyses were performed to assess the associations between AS events and the overall survival (OS) rates of patients with CCA. Additional multivariate Cox regression analyses were used to identify AS events that were significantly associated with prognosis, which were used to construct a prediction model with a prognostic index (PI). A receiver operating characteristic (ROC) curve was used to determine the predictive value of the PI, and Pearson's correlation analysis was used to determine the association between OS-related AS events and splicing factors. A total of 38,804 AS events were identified in 9,673 CCA genes, among which univariate Cox regression analysis identified 1,639 AS events associated with OS (P<0.05); multivariate Cox regression analysis narrowed this list to 23 CCA AS events (P<0.001). The final PI model was constructed to predict the survival of patients with CCA; the ROC curve demonstrated that it had a high predictive power for CCA prognosis, with a highest area under the curve of 0.986. Correlations between 23 OS-related AS events and splicing factors were also noted, and may thus, these AS events may be used to improve predictions of OS. In conclusion, AS events exhibited potential for predicting the prognosis of patients with CCA, and thus, the effects of AS events in CCA required further examination.

Down-regulation and clinical significance of miR-7-2-3p in papillary thyroid carcinoma with multiple detecting methods.

Altered miRNA expression participates in the biological progress of thyroid carcinoma and functions as a diagnostic marker or therapeutic agent. However, the role of miR-7-2-3p is currently unclear. The authors' study was the first investigation of miR-7-2-3p expression level and diagnostic ability in several public databases. Potential target genes were obtained from DIANA Tools, and function enrichment analysis was then performed. Furthermore, the authors examined expression levels of potential targets in the Human Protein Atlas (HPA) and the Cancer Genome Atlas (TCGA). Finally, the potential transcription factors (TFs) were predicted by JASPAR. TCGA, GSE62054, GSE73182, GSE40807, and GSE55780 revealed that miR-7-2-3p expression in papillary thyroid carcinoma (PTC) tissues was notably lower compared with non-tumour tissues, while its expression in E-MATB-736 showed no remarkable difference. Function enrichment analysis showed that 698 genes were enriched in pathways, including pathways in cancer, and glioma. CCND1, GSK3B, and ITGAV of pathways in cancer were inverse correlations with miR-7-2-3p in both post-transcription and protein levels. According to the TF prediction, the prospective upstream TFs of miR-7-2-3p were ISX, SPI1, PRRX1, and BARX1. MiR-7-2-3p was significantly down-regulated and may act on PTC progression by crucial pathways. However, the mechanisms of miR-7-2-3p need further investigation.

Prognostic index of aberrant mRNA splicing profiling acts as a predictive indicator for hepatocellular carcinoma based on TCGA SpliceSeq data.

Alternative splicing in tumor cells may be used as a molecular marker for the differential diagnosis of certain tumor types and assessment of prognosis. The aim of the present study was to investigate the associations among alternative splicing events, splicing factors, and the survival of patients with hepatocellular carcinoma (HCC). The alternative splicing event profiles of 371 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) SpliceSeq data, and the percent­splice­in value for each splicing event was calculated. The association between alternative splicing events and overall survival was evaluated. The most significant prognosis­related splicing events were used to build up a prognostic index (PI). A total of 3,082 survival­associated alternative splicing events were detected in HCC. The final PI based on all of the most significant candidate alternative splicing events exhibited better performance in distinguishing good or poor survival in patients compared to the PI based on a single type of splicing event. Receiver operating characteristic curves confirmed the high efficiency of the PI in predicting the survival of HCC patients, with an area under the curve of 0.914. The overexpression of 32 prognosis­related splicing factor genes could also predict poor prognosis in patients with HCC. In conclusion, the constructed computational prognostic model based on HCC­specific alternative splicing events may be used as a molecular marker for the prognosis of HCC.

Evaluation of miR-302b-5p expression and molecular mechanism in hepatocellular carcinoma: Findings based on RT-qPCR and in silico analysis.

BACKGROUND AND AIM: Extensive research has revealed that microRNAs (miRNAs) play a principle role in cancer, and miRNAs associated with specific cancers have also been identified. The role of microRNA (miR)-302b-5p, which is one of the miRNAs reported in association with cancer, in hepatocellular carcinoma (HCC) is still unclear. Thus, the present study aimed to reveal the expression and potential molecule mechanism of miR-302b-5p in HCC. METHODS: An extensive meta-analysis of data from real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR), Gene Expression Omnibus and ArrayExpress microarrays was used to determine the expression of miR-302b-5p in HCC tissue samples and non-cancerous liver tissue samples. The sensitivity and specificity of miR-302b-5p as an indicator of HCC was estimated by plotting the receiver operating characteristic (ROC) and summarized ROC (sROC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to unravel the molecular mechanisms and biological functions of miR-302b-5p in HCC. Further, the putative target genes of miR-302b-5p were harvested based on the predicted genes and differentially expressed genes in HCC. Finally, the protein-protein interaction (PPI) network was built to determine the hub genes. RESULTS: According to the RT-qPCR results, the expression of miR-302b-5p was pronouncedly decreased in 39 HCC tissue samples as compared to 39 non-cancerous liver tissue samples. The standard mean difference (SMD) values of all the samples used in the meta-analysis also indicated lower miR-302b-5p expression in the 558 HCC tissue samples than in the 286 non-cancerous liver tissue samples. ROC and sROC analyses showed that miR-302b-5p had good specificity and sensitivity for distinguishing HCC tissue from non-cancerous liver tissue. Bioinformatics analyses identified 227 putative genes, and these genes were evidently enriched in the processes of organelle fission, chromosome and chromatin binding and were centralized in a "lysosome" pathway. The PPI network indicated that DNA topoisomerase II alpha (TOP2 A) was the most prominent hub gene of miR-302b-5p in HCC. Interestingly, according to the TCGA and Genotype-Tissue Expression databases, the mRNA and protein expression of TOP2 A were both elevated in HCC tissue samples as compared to non-cancerous liver tissue samples, and the overall survival and disease-free survival revealed that a high level of TOP2 A might reflect poor HCC outcome. CONCLUSIONS: Our findings indicate that miR-302b-5p might suppress HCC progression, and TOP2 A might be a potential target of miR-302b-5p in HCC. However, in-depth in vivo and in vitro experiments are required to verify these findings and explore the mechanisms involved.

Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.

BACKGROUND: The present study attempted to identify potential key genes and miRNAs of dyslipidemia in obese, and to investigate the possible mechanisms associated with them. METHODS: The microarray data of GSE66676 were downloaded, including 67 obese samples from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network (WGCNA) analysis was performed using WGCNA package and grey60 module was considered as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for this module were performed by clusterProfiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using molecular complex detection. RESULTS: Collagen type I alpha 1 chain gene (COL1A1) had the best significant meaning. After bioinformatic analysis, we identified four miRNAs (hsa-miR-3659, hsa-miR-4658, hsa-miR151a-5p and hsa-miR-151b) which can bind SNPs in 3'UTR in COL1A1. After validation with RT-qPCR, only two miRNAs (hsa-miR-3659 and hsa-miR151a-5p) had statistical significance. CONCLUSIONS: The area of 0.806 for miR-3659 and 0.769 for miR-151a-5p under the ROC curve (AUC) may have good diagnostic value for dyslipidemia. Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.

Elevation of miR-191-5p level and its potential signaling pathways in hepatocellular carcinoma: a study validated by microarray and in-house qRT-PCR with 1,291 clinical samples.

BACKGROUND: The miR-191-5p expression has been reported to increase in hepatocellular carcinoma (HCC), but its clinical value and exact role remain to be further clarified. Thus, a comprehensive analysis was performed in the current study to explore the underlying function of miR-191-5p in HCC. METHODS: HCC-related expression data were collected to conduct a thorough analysis to determine the miR-191-5p expression and its clinical significance in HCC, including microarray data from the Gene Expression Omnibus and ArrayExpress database as well as quantitative real-time polymerase chain reaction (qRT-PCR) data of 178 matched clinical samples. The underlying relationship between miR-191-5p and HCC was also explored on the basis of a series of bioinformatics analyses. RESULTS: The overall pooled meta-analysis showed an overexpression of miR-191-5p in the HCC samples (SMD=0.400, 95% CI=0.139-0.663, P=0.003), consistent with the detected result of the clinical HCC samples through the qRT-PCR analysis. Higher miR-191-5p levels were correlated with advanced TNM stages (III and IV), higher pathological grades, and metastasis. Functionally, 64 potential target genes were acquired for further mechanism analysis. Two pathways (p75 neurotrophin receptor and liver kinase B1-mediated signaling pathways), which were likely modulated by miR-191-5p, were regarded to be linked to the deterioration of HCC. Early growth response 1 and UBE2D3 were identified as the most likely targets for miR-191-5p in HCC and were commonly implied in the top enriched pathways and protein-protein network. CONCLUSIONS: In summary, miR-191-5p may function as a tumor promoter miRNA of HCC, and the miR-191-5p inhibitor may contribute to the targeted HCC treatment in the future.

Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Hyperlipidemia.

BACKGROUND/AIMS: The present study attempted to identify the potential key genes and pathways of hyperlipidemia, and to investigate the possible mechanisms associated with them. METHODS: The array data of GSE3059 were downloaded, including thirteen samples of hyperlipidemia from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was performed with WGCNA package, and the salmon and midnight blue modules were found as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these two modules were performed by cluster Profiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection. RESULTS: Five genes (histone deacetylase 4, HDAC4; F2R like trypsin receptor 1, F2RL1; abhydrolase domain containing 2, ABHD2; transmembrane 4 L six family member 1, TM4SF1; and family with sequence similarity 13-member A, FAM13A) were found with a significant meaning. When their expression levels were validated with RT-qPCR, the relative expression levels were lower (HDAC4) and higher (F2RL1, ABHD2, TM4SF1 and FAM13A) in hyperlipidemia than in normal controls (P < 0.05-0.01). Subgroup analysis showed that the relative expression levels of HDAC4 were lower, whereas those of F2RL1 and ABHD2 were higher in Maonan than in Han ethnic groups (P < 0.05). CONCLUSION: Except for genetic factors and environmental exposures, epigenetic influence was another mechanism of hyperlipidemia in our study populations, which needed to further confirm.

Association of the APOA1 rs964184 SNP and serum lipid traits in the Chinese Maonan and Han populations.

BACKGROUND: Maonan nationality belongs to a mountain ethnic minority in China. Little is known about the association of apolipoprotein A1 gene (APOA1) rs964184 single nucleotide polymorphism (SNP) and serum lipid levels in this population. The aim of this study was to detect the association of the APOA1 rs964184 SNP and several environmental factors with serum lipid profiles in the Chinese Maonan and Han populations. METHODS: Genotypes of the APOA1 rs964184 SNP in 867 individuals of Maonan nationality and 820 participants of Han nationality were determined by polymerase chain reaction and restriction fragment length polymorphism, combined with gel electrophoresis, and confirmed by direct sequencing. RESULTS: The frequencies of CC, CG and GG genotypes of the APOA1 rs964184 SNP were 68.86, 29.18 and 1.96% in the Maonan population, and 63.78, 30.85 and 5.37% in the Han population (P < 0.001). The frequency of the G allele was 16.55% in Maonan and 20.79% in Han (P < 0.001). The G allele carriers had lower high-density lipoprotein cholesterol (HDL-C) levels in Maonan and higher triglyceride (TG) levels in Han peoples than the G allele non-carriers. Subgroup analyses showed that the G allele carriers had lower HDL-C levels in both Maonan males and females; and lower apolipoprotein (Apo) A1 levels and the ApoA1/ApoB ratio in Han males than the G allele non-carriers. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. CONCLUSIONS: The present study reveals that there may be a racial/ethnic- and/or gender-specific association between the APOA1 rs964184 SNP and serum lipid parameters in our study populations. TRIAL REGISTRATION: Retrospectively registered.

BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia.

Little is known about the association of the BCL3-PVRL2-TOMM40 SNPs and dyslipidemia. This study was to detect 12 BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia in the Chinese Maonan population. Genotyping was performed in 1130 normal and 832 dyslipidemia participants. Generalized multifactor dimensionality reduction was used to screen the best interaction combination among SNPs and environmental exposures. Allele and genotype frequencies of the detected SNPs were different between the two groups (P < 0.05-0.001). Association of the 12 SNPs and serum lipid levels was observed (P < 0.004-0.001). Multiple-locus linkage disequilibrium was not statistically independent in the population (D' = 0.01-0.98). The dominant model of rs8100239 and rs157580 SNPs, several haplotypes and G × G interaction haplotypes contributed to a protection, whereas the dominant model of rs10402271, rs3810143, rs519113, rs6859 SNPs, another haplotypes and G × G interaction haplotypes revealed an increased morbidity function (P < 0.05-0.001). There were significant three-locus model involving SNP-SNP, SNP-environment, haplotype-haplotype interactions (P < 0.05-0.001). The subjects carrying several genotypes and haplotypes decreased dyslipidemia risk, whereas the subjects carrying other genotypes and haplotypes increased dyslipidemia risk. The BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia were observed in the Chinese Maonan population.

Insulin-like factor-2 receptor rs9456497 G genotype overrepresents in males of average population and its correlation with cardiovascular risks.

OBJECTIVES: To look at the possible effect of IGF2R rs9456497 on cardiovascular risks in a long-lived population. METHODS: IGF-2R rs9456497 was genotyped by iMLDR for 496 long-lived Zhuang Chinese (90-107 y/o) and their offspring (n = 723, 60-75 y/o) and healthy controls (n = 611, 60-75 y/o). Association analyses were then conducted among genotypes and cardiovascular risks. RESULTS: The G genotype (GA/GG) was found to represent more frequently in males of general population. No significantly difference was detected among genotypes in each group except that G genotype tended to reduce the systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in longevity group. However, after sex stratification, total cholesterol (TC) of each genotype in offspring males was elevated versus relevant genotype in longevity and control group; the triglyceride (TG), fasting plasma glucose (FPG) and BMI of each genotype in longevity group were lower while SBP and DBP were higher than that of the relevant genotype in offspring and controls. After stratified by lipid status, the frequency of G allele was markedly increased in the dyslipidemic subgroup in the combined population and controls. Linear regressive analyses showed that HDL was positively correlated to rs9456497 GA genotype while BMI was negatively correlated to AA genotype in offspring group, whereas TC and TG were reversely while BMI was positively associated with AA genotype in CG. CONCLUSIONS: IGF-2R rs9456497 G genotype correlates to detrimental cardiovascular risks in ordinary population which might partially interpret their less preservation of health as compared to long-lived cohort.

Association of BDNF rs11030104 SNP and serum lipid levels in two Chinese ethnic groups.

The correlation between the BDNF rs11030104 single nucleotide polymorphism (SNP) and serum lipid levels has been understudied. The present study was conducted to detect the association of the BDNF rs11030104 SNP and several environmental factors with serum lipid levels in the Jing and Han nationalities. Genotypes of the BDNF rs11030104 SNP in 709 unrelated subjects of Han and 706 unrelated participants of Jing populations were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and further verified by direct sequencing. There was no significant difference in either genotypic or allelic frequencies between the Han and Jing populations. The genotypic and allelic frequencies of the SNP in Jing but not in Han populations were different between male and female subgroups (P<0.05 for each). The levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the Jing population were different among the genotypes, the G allele carriers had lower TC and LDL-C levels than the G allele non-carriers. Subgroup analyses showed that the differences in serum TC and LDL-C levels among the genotypes were observed in the Jing males but not in females. Serum lipid profiles were also significantly associated with some environmental factors in the Han and Jing populations, or in male and female subgroups of the two ethnic groups (P<0.05 for all). Our study exhibited a correlation between the BDNF rs11030104 SNP and serum TC and LDL-C levels in the Jing males. These results indicate that there may be a racial/ethnic- and/or sex-specific association of the BDNF rs11030104 SNP and serum lipid parameters.