The lipid peroxidation-derived DNA adduct γ-OHPdG as a diagnostic and prognostic biomarker in hepatocellular carcinoma.

PURPOSE: Chronic inflammation and lipid peroxidation (LPO) are associated with the pathogenesis of hepatocellular carcinoma (HCC), and γ-hydroxy-1, N2-propanodeoxyguanosine (γ-OHPdG) is a promutagenic DNA adduct derived from LPO. This study aimed to examine the relationship between γ-OHPdG and the progression of liver carcinogenesis. METHODS: Primary HCC specimens were obtained from 228 patients and cirrhosis specimens from 46 patients. The patients were followed up with after surgery via outpatient visits and telephone calls. The levels of γ-OHPdG were determined by immunohistochemical analysis in the carcinomatous tissues together with adjacent and cirrhosis tissues. RESULTS: γ-OHPdG levels in the cancerous tissues were significantly higher compared to adjacent tissues (P < 0.001) and also higher than the ones from the tissues of cirrhosis patients. Along with tumor size, histological grade, MVI grade, T stage, the percentage of ki67-positive cells and HCC progression, γ-OHPdG levels in cancerous tissues showed a gradually increasing trend. Moreover, prognostic analysis showed that higher γ-OHPdG levels in cancerous tissues were strongly correlated with lower overall survival (P < 0.001), lower intrahepatic recurrence-free survival (P < 0.001) and lower distant metastasis-free survival (P < 0.05). There was a trend, although not statistically significant, of increased levels of γ-OHPdG in cirrhosis cases that advanced to HCC, whereas γ-OHPdG levels reversely correlated with the period of time observed for cirrhosis advanced to HCC. CONCLUSIONS: These results suggest that γ-OHPdG is a prognostic biomarker for predicting outcomes in HCC, and may serve as a prospective indicator for predicting HCC in cirrhosis patients.

High-throughput screening of 756 chemical contaminants in aquaculture products using liquid chromatography/quadrupole time-of-flight mass spectrometry.

A high-throughput screening method embracing 756 multiclass chemical contaminants in aquaculture products was developed using modified QuEChERS extraction coupled with liquid chromatography/quadrupole time-of-flight mass spectrometry. A mega-database with retention time/accurate mass data for 524 pesticides, 182 veterinary drugs, 32 persistent organic pollutants and 18 marine toxins was established for compound identification via retrospective library searching. In the four representative matrices (muscle tissues of tilapia and grouper, and edible portions of oyster and scallop), all the database compounds showed acceptable recovery and repeatability with the screening detection limit and limit of quantification below 0.01 mg/kg for >90% of them. The matrix-matched calibration revealed acceptable quantitative property of the method in terms of linear range, linearity, and matrix effect, and fish muscle samples showed stronger matrix effect than shellfish samples. Analysis of 64 real-life samples from aquaculture farms and retail markets evidenced applicability of the proposed method to high-throughput screening scenarios.

Metformin Inhibited Proliferation and Metastasis of Colorectal Cancer and presented a Synergistic Effect on 5-FU.

The purpose of this study was to investigate the effect of metformin or the combination of metformin and 5-FU on the growth and metastasis of colorectal cancer (CRC). For the in vitro experiments, HCT 116 and SW1463 cell lines were treated with metformin or the combination of metformin and 5-FU. Cell proliferation and invasion were analyzed by CCK-8, colony formation, and transwell assay, respectively. For the in vivo experiments, the CRC xenograft nude mice model was used to observe the effects of metformin or combined with 5-FU on tumor growth and metastasis. Metformin significantly inhibited the proliferation and invasion of HCT116 and SW1463 cells in vitro, which showed synergetic effects to 5-FU. In CRC xenograft nude mice, metformin alone and metformin combined with 5-FU treatment significantly inhibited tumor cell proliferation and tumor metastasis. In summary, metformin played an inhibitory role in the proliferation and metastasis of CRC and had a synergistic effect with 5-FU. Metformin may be a potentially effective anti-metastatic drug or an anticancer adjuvant agent for treating CRC.

MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1.

Background: MicroRNAs (miRNAs) could modulate gene expression at the posttranscriptional level by promoting mRNA degradation or blocking mRNA translation, thus affecting the occurrence and development of cancer. Methods: In this work, qRT-PCR was conducted to detect the expression of miR-193a-3p and CCND1. The ability of cell proliferation was evaluated via CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Bioinformatic techniques were employed to research the regulatory relationship between miR-193a-3p and target genes. The relationship between miR-193a-3p and CCND1 was verified via dual-luciferase reporter assays. Results: MiR-193a-3p expression in pancreatic ductal adenocarcinoma (PDAC) tissue was significantly lower than in non-cancerous tissue. After overexpressing miR-193a-3p in PDAC cells, their multiplication ability was significantly inhibited, apoptosis was accelerated, and the cell cycle was blocked in the G1 and G2/M phases. CCND1 was confirmed to have a targeted relationship with miR-193a-3p. Moreover, CCND1 expression was significantly lower in PDAC cells with an overexpression of miR-193a-3p. Conclusions: MiR-193a-3p targeted CCND1 to suppress tumor growth in PDAC cells. MiR-193a-3p may function as a tumor inhibitor in PDAC development, which could offer a promising therapeutic and prognostic strategy for PDAC treatment.

Biological Effect and Mechanism of the miR-23b-3p/ANXA2 Axis in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIMS: Accumulating evidence strongly suggests that microRNAs (miRNAs) modulate the expression of known tumor suppressor genes and oncogenes. In the present study, we found that the proliferation and invasion ability of pancreatic ductal adenocarcinoma (PDAC) cells were significantly suppressed by the overexpression of miR-23b-3p. In addition, there are miR-23b-3p binding sites in annexin A2 (ANXA2). Here, we investigated whether miR-23b-3p had an impact on the progression and metastasis of PDAC by targeting ANXA2. METHODS: Cell proliferation, migration, and invasion, and cell cycle assays were performed to explore the effect of miR-23b-3p on various malignant phenotypes of pancreatic cancer cells. The size of tumors was observed following miR-23b-3p overexpression in an in vivo chick chorioallantoic membrane assay. Dual-luciferase reporter, quantitative real-time PCR, western blot, and immunohistochemical analyses were used to validate the relationship between miR-23b-3p and ANXA2 in vitro. RESULTS: We observed that miR-23b-3p could bind specifically to the 3' untranslated region of ANXA2 and inhibit its expression. MiR-23b-3p overexpression downregulated the expression of ANXA2 mRNA in PDAC cells and limited the size of tumors or even prevented tumor formation. In addition, there was a negative correlation between miR-23b-3p expression and ANXA2 protein expression in clinical specimens. CONCLUSION: MiR-23b-3p inhibits the development and progression of PDAC by regulating ANXA2 directly.

A meta-analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR-193a-5p in lung cancer.

Lung cancer is a leading cause of mortality worldwide and despite recent improvements in lung cancer treatments patient mortality remains high. miR-193a-5p serves a crucial role in the initiation and development of cancer; it is necessary to understand the underlying molecular mechanisms of miR-193a-5p in lung cancer, which may enable the development of improved clinical diagnoses and therapies. The present study investigated the diagnostic value of peripheral blood and tissue miR-193a-5p expression using a microarray meta-analysis. Peripheral blood miR-193a-5p was revealed to be upregulated in patients with lung cancer. The pooled area under the curve (AUC) was 0.67, with a sensitivity and specificity of 0.74 and 0.56, respectively. Conversely, the peripheral tissue miR-193a-5p expression in patients with lung cancer was significantly downregulated. The pooled AUC was 0.83, and the sensitivity and specificity were 0.65 and 0.89, respectively. Through bioinformatics analysis, three Kyoto Encyclopedia of Genes and Genomes (KEGG) terms, pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway, were identified as associated with miR-193a-5p in lung cancer. In addition, in lung cancer, six key miR-193a-5p target genes, receptor tyrosine-protein kinase erbB-2 (ERBB2), nuclear cap-binding protein subunit 2 (NCBP2), collagen α-1(I) chain (COL1A1), roprotein convertase subtilisin/kexin type 9 (PCSK9), casein kinase II subunit α (CSNK2A1) and nucleolar transcription factor 1 (UBTF), were identified, five of which were significantly upregulated (ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF). The protein expression of ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF was also upregulated. NCBP2 and CSNK2A1 were negatively correlated with miR-193a-5p. The results demonstrated that miR-193a-5p exhibited opposite expression patterns in peripheral blood and tissue. Upregulated peripheral blood miR-193a-5p and downregulated tissue miR-193a-5p may be promising diagnostic biomarkers in lung cancer. In addition, the KEGG terms pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway may suggest which pathways serve vital roles in lung cancer by regulating miR-193a-5p. In addition, six genes, ERBB2, COL1A1, PCSK9, UBTF and particularly NCBP2 and CSNK2A1, may be key target genes of miR-193a-5p in lung cancer.

Biological function of UCA1 in hepatocellular carcinoma and its clinical significance: Investigation with in vitro and meta-analysis.

Urothelial cancer associated 1 (UCA1) was upregulated in hepatocellular carcinoma (HCC) tissues and cell lines, and the expression of UCA1 was associated with several clinical features and malignant behaviours in HCC. However, none of these findings completely interpreted the role of UCA1 in HCC. We conducted this investigation to validate the expression of UCA1 and its relationship with Tumor Node Metastasis (TNM) stage in 41 HCC tissues and their paired noncancerous adjacent tissues by real-time qPCR. Furthermore, we also explored the biological functions of UCA1 in vitro with HCC cell lines. Most importantly, we conducted a comprehensive meta-analysis and bioinformatics investigation based on peer-reviewed literature and in silico approaches to further summarise the clinical value and functions of UCA1 in HCC. UCA1 expression was remarkably upregulated in HCC tissues, and its expression was profoundly higher in advanced stages than in early stages. Reducing the expression levels of UCA1 suppressed the proliferation and induced apoptosis of HCC cells. Furthermore, the present meta-analysis validated that up-regulated UCA1 was closely related to larger tumour size and advanced TNM stages, and the overexpression of UCA1 was significantly correlated with a shorter OS. Additionally, according to GO analysis, the target genes were found concentrated in the following biological processes: extracellular matrix organisation, cilium assembly and cilium morphogenesis. KEGG pathway analysis showed that the UCA1-related genes were significantly enriched in the following pathways: hippo signalling pathway, bile secretion and gastric acid secretion. This evidence hinted that UCA1 could play an indispensable proliferation-related key role in HCC via the hippo signalling pathway. However, the exact molecular mechanism needs to be verified with future functional experiments.

Clinical significance of high expression of miR-452-5p in lung squamous cell carcinoma.

The role of microRNA (miRNA)-452-5p in lung squamous cell carcinoma (LUSC) remains unclear. Therefore, the present systematic study was performed to investigate the clinical significance and the rudimentary mechanism of the function of miR-452-5p in LUSC. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to confirm the expression level and clinical value of miR-452-5p in LUSC. Using online databases and bioinformatic software, gene ontology (GO), pathway and protein-protein interaction (PPI) analyses of miR-452-5p target genes were performed to examine the molecular mechanism of miR-452-5p. The association between the expression of miR-452-5p and that of its hub genes was verified using TCGA. Based on TCGA data on 387 clinical specimens, the expression of miR-452-5p in LUSC was significantly increased compared with adjacent lung tissues (7.1525±1.39063 vs. 6.0885±0.35298; P<0.001). The expression levels of miR-452-5p were significantly correlated with age (P=0.001) and tumor-node metastasis stage (P=0.028). Furthermore, the increased expression of miR-452-5p in LUSC compared with non-cancerous tissue [standard mean deviation (SMD), 0.372; 95% confidence interval (CI), 0.020-0.724; z=2.07; P=0.038] was validated by a meta-analysis of 720 clinical samples. The GO and pathway analyses revealed that miR-452-5p target genes were mainly enriched in the 'regulation of transcription', 'nucleoplasm', 'protein binding' and 'cell cycle' pathways. A total of 10 hub genes were identified by PPI analysis, and 5 hub genes (SMAD4, SMAD2, CDKN1B, YWHAE and YWHAB) were significantly enriched in the 'cell cycle' pathway. The expression of CDKN1B was negatively correlated with miR-452-5p (P=0.003). It was concluded that miR-452-5p may serve an essential role in the occurrence and progression of LUSC by targeting CDKN1B, which is involved in the cell cycle.

Clinical value of miR-182-5p in lung squamous cell carcinoma: a study combining data from TCGA, GEO, and RT-qPCR validation.

BACKGROUND: MiR-182-5p, as a member of miRNA family, can be detected in lung cancer and plays an important role in lung cancer. To explore the clinical value of miR-182-5p in lung squamous cell carcinoma (LUSC) and to unveil the molecular mechanism of LUSC. METHODS: The clinical value of miR-182-5p in LUSC was investigated by collecting and calculating data from The Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus (GEO) database, and real-time quantitative polymerase chain reaction (RT-qPCR). Twelve prediction platforms were used to predict the target genes of miR-182-5p. Protein-protein interaction (PPI) networks and gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the molecular mechanism of LUSC. RESULTS: The expression of miR-182-5p was significantly over-expressed in LUSC than in non-cancerous tissues, as evidenced by various approaches, including the TCGA database, GEO microarrays, RT-qPCR, and a comprehensive meta-analysis of 501 LUSC cases and 148 non-cancerous cases. Furthermore, a total of 81 potential target genes were chosen from the union of predicted genes and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in pathways related to biological processes. PPIs revealed the relationships between these genes, with EPAS1, PRKCE, NR3C1, and RHOB being located in the center of the PPI network. CONCLUSIONS: MiR-182-5p upregulation greatly contributes to LUSC and may serve as a biomarker in LUSC.

Clinical value of miR-198-5p in lung squamous cell carcinoma assessed using microarray and RT-qPCR.

BACKGROUND: To examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC). METHODS: Gene Expression Omnibus (GEO) microarray datasets were used to explore the miR-198-5p expression and its diagnostic value in LUSC. Real-time reverse transcription quantitative polymerase chain reaction was used to evaluate the expression of miR-198-5p in 23 formalin-fixed, paraffin-embedded (FFPE) LUSC tissues and corresponding non-cancerous tissues. The correlation between miR-198-5p expression and clinic pathological features was assessed. Meanwhile, putative target messenger RNAs of miR-198-5p were identified based on the analysis of differentially expressed genes in the Cancer Genome Atlas (TCGA) and 12 miRNA prediction tools. Subsequently, the putative target genes were sent to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. RESULTS: MiR-198-5p was low expressed in LUSC tissues. The combined standard mean difference (SMD) values of miR-198-5p expression based on GEO datasets were - 0.30 (95% confidence interval (CI) - 0.54, - 0.06) and - 0.39 (95% CI - 0.83, 0.05) using fixed effect model and random effect model, respectively. The sensitivity and specificity were not sufficiently high, as the area under the curve (AUC) was 0.7749 (Q* = 0.7143) based on summarized receiver operating characteristic (SROC) curves constructed using GEO datasets. Based on the in-house RT-qPCR, miR-198-5p expression was 4.3826 ± 1.7660 in LUSC tissues and 4.4522 ± 1.8263 in adjacent normal tissues (P = 0.885). The expression of miR-198-5p was significantly higher in patients with early TNM stages (I-II) than that in cases with advanced TNM stages (III-IV) (5.4400 ± 1.5277 vs 3.5690 ± 1.5228, P = 0.008). Continuous variable-based meta-analysis of GEO and PCR data displayed the SMD values of - 0.26 (95% CI - 0.48, - 0.04) and - 0.34 (95% CI - 0.71, 0.04) based on fixed and random effect models, respectively. As for the diagnostic value of miR-198-5p, the AUC based on the SROC curve using GEO and PCR data was 0.7351 (Q* = 0.6812). In total, 542 genes were identified as the targets of miR-198-5p. The most enriched Gene Ontology terms were epidermis development among biological processes, cell junction among cellular components, and protein dimerization activity among molecule functions. The pathway of non-small cell lung cancer was the most significant pathway identified using Kyoto Encyclopedia of Genes and Genomes analysis. CONCLUSION: The expression of miR-198-5p is related to the TNM stage. Thus, miR-198-5p might play an important role via its target genes in LUSC.

The clinical value of miR-193a-3p in non-small cell lung cancer and its potential molecular mechanism explored in silico using RNA-sequencing and microarray data.

miR-193a-3p is a tumor-related miRNA playing an essential role in tumorigenesis and progression of non-small cell lung cancer (NSCLC). The objective of the present study was to investigate the relationship between miR-193a-3p expression and clinical value and to further explore the potential signaling of miR-193a-3p in the carcinogenesis of NSCLC. RNA-sequencing and microarray data were collected from the databases GEO, ArrayExpress and The Cancer Genome Atlas (TCGA). Furthermore, in silico assessments were performed to analyze the prospective pathways and networks of the target genes of miR-193a-3p. In total, 453 cases of NSCLC patients and 476 normal controls were included in blood samples, while 920 cases of NSCLC patients and 406 normal controls were included in tissue samples. The pooled positive likelihood ratio, the pooled negative likelihood ratio and the pooled diagnostic odds ratio were calculated to reflect the diagnostic value of miR-193a-3p in blood and tissue samples. Moreover, the areas under the curve of the summary receiver operating characteristic curve of blood and tissue were 0.64 and 0.79, respectively. In addition, we found a lower level of miR-193a in NSCLC tissues than in non-cancerous controls based on TCGA. A gene ontology (GO) enrichment analysis demonstrated that miR-193a-3p could be related to key signaling pathways in NSCLC. Also, several vital pathways were illustrated by KEGG. Lower expression of miR-193a-3p in tissue samples of NSCLC may be associated with tumorigenesis and be a predictor of deterioration of NSCLC patients, and pathway analysis revealed crucial signaling pathways correlated with the incidence and progress of NSCLC.

Clinical implication of UCA1 in non-small cell lung cancer and its effect on caspase-3/7 activation and apoptosis induction in vitro.

Since urothelial cancer associated 1 (UCA1) was discovered in human bladder cancer, it has been reported to be dysregulated expressed in various kinds of solid tumors. But the clinical role and the function of UCA1 in non-small cell lung cancer (NSCLC) remains incompletely understood. In this study, we mined the data of UCA1 expression in NSCLC from Oncomine, Gene expression profiling interactive analysis (GEPIA) and cBioPortal to analyze the contribution of UCA1 in the cancer initiation and progression of NSCLC. We also performed a series of in vitro experiments by using NSCLC cells to confirm the biological function of UCA1 in NSCLC, especially its effect on caspase-3/7 activity and apoptosis through RNA interference experiment. From Oncomine, the UCA1 levels were both up-regulated in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC), as compared to non-cancerous controls. Higher levels of UCA1 pointed to a poorer overall survival in NSCLC, with the HR being 1.3. Only two genetic alterations, including amplification and deep deletion, were observed for UCA1 as provided by cBioPortal. Both MTS and Cell Titer-blue assays showed an accordant inhibitory effect of UCA1 siRNAs on the cell growth. In conclusion, lncRNA UCA1 might play a substantial role in the occurrence and development of NSCLC, especially in LUAD patients, which is partly due to its effect on caspase-3/7 activity suppression.

Prediction of clinical outcome and survival in soft-tissue sarcoma using a ten-lncRNA signature.

The prognostic value of long non-coding RNAs (lncRNAs) in patients with soft-tissue sarcoma has rarely been unraveled. The aim of the study was to find a lncRNA signature to predict the clinical outcome and survival in soft-tissue sarcoma based on the high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA) database. The lncRNAs which closely correlated with overall survival in 258 soft-tissue sarcoma patients were identified with Cox proportional regression model. Ten lncRNAs, including RP11-560J1.2, AP001432.14, RP4-665J23.1, LINC00680, AC006129.2, RP11-230G5.2, BACH1-IT2, RP11-274B21.9, RP11-504A18.1 and RP11-713P17.3, were selected to calculate a risk score. The risk score could effectively predict patients' outcome, such as the status of mitotic count of tumor cells, person neoplasm cancer and residual tumor. More inspiringly, the risk score generated from the 10-lncRNA signature was an independent prognostic indicator for soft-tissue sarcoma patients. Overall, this 10-lncRNA signature gains the potential as an effective prognostic tool for soft-tissue sarcoma as part of the integrated clinical RNA-seq program.

Clinical roles of the aberrantly expressed lncRNAs in lung squamous cell carcinoma: a study based on RNA-sequencing and microarray data mining.

Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of lung cancer and there have been few therapeutic alternatives for recurrent LUSC due to the lack of specific driver molecules. To investigate the prospective role of lncRNAs in the tumorigenesis and progression of LUSC, the aberrantly expressed lncRNAs were calculated based on The Cancer Genome Atlas RNA-seq data. Of 7589 lncRNAs with 504 LUSC cases, 884 lncRNAs were identified as being aberrantly expressed (|log2 fold change| >2 and adjusted P<0.05) by DESeq R. The top 10 lncRNAs with the highest diagnostic value were SFTA1P,LINC00968, LINC00961, LINC01572,RP1-78O14.1, FENDRR, LINC01314,LINC01272, GATA6-AS1, and MIR3945HG. In addition to the significant roles in the carcinogenesis of LUSC, several lncRNAs also played vital parts in the survival and progression of LUSC. SFTA1P, LINC01272, GATA6-AS1 and MIR3945HG were closely related to the survival time of LUSC. Furthermore, LINC01572 and LINC01314 could distinguish the LUSC at early stage from that at advanced stage. The prospective molecular assessment of key lncRNAs showed that a certain series of genes could be involved in the regulation network. Furthermore, the OncoPrint from cBioPortal indicated that 14% (69/501) LUSC cases with genetic alterations could be obtained, including amplification, deep deletion and mRNA upregulation. More interestingly, the cases with genetic alterations had a poorer survival as compared to those without alterations. Overall, the study propounds a potentiality for interpreting the pathogenesis and development of LUSC with lncRNAs, and provides a novel platform for searching for more capable diagnostic biomarkers for LUSC.

Identification of a RNA-Seq based prognostic signature with five lncRNAs for lung squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) expression profile signature for survival assessment in lung squamous cell carcinoma (LUSC) are largely inconsistent due to distinct detecting approaches and small sample size. Systematic and integrative investigation of RNA-Seq based data from The Cancer Genome Atlas (TCGA) herein was performed to determine candidate lncRNAs for prognosis evaluation of LUSC. A total of 60483 genes, including 7589 lncRNAs were assessed in a cohort including 478 LUSC cases with follow-up data. Firstly, 4225 differentially expressed lncRNAs were obtained via R packages. Next, univariate and multivariate Cox proportional hazards regression revealed that 41 lncRNAs were closely related to the survival of LUSC. Finally, lncRNA based prognosis index (PI) could predict overall survival of LUSC with high accuracy (AUC = 0.652, CI: 0.598, 0.705), PI = expCYP4F26P*ßCYP4F26P+expRP11-108M12.3*ßRP11-108M12.3+expRP11-38M8.1*ßRP11-38M8.1+expRP11-54H7.4*ßRP11-54H7.4+expZNF503-AS1*ßZNF503-AS1. Furthermore, it was confirmed that the five-lncRNA signature could act as an independent prognostic indicator for LUSC (HR = 2.068, p < 0.001 with univariate analysis, HR = 1.928, p = 0.038 with multivariate). Besides, we constructed a weighted gene co-expression network analysis (WGCNA) of key lncRNA RP11-54H7.4 according to the p-value of related genes' weight. This study provides a RNA-Seq based prognostic signature with five lncRNAs for further clinical application to LUSC patients.

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases.

PURPOSE: Long noncoding RNAs (lncRNAs) are known to function as regulators in the development and occurrence of various tumors. MALAT1 is a highly conserved lncRNA and has vital functions in diverse tumors, including pancreatic cancer (PC). However, the underlying molecular regulatory mechanism involved in the occurrence and development of PC remains largely unknown. Thus, it is important to explore MALAT1 in PC and elucidate its function, which might offer a new perspective for clinical diagnosis and therapy. METHODS: First, we used the Gene Expression Omnibus, Oncomine, and The Cancer Genome Atlas databases to determine the clinical diagnostic and prognostic values of MALAT1. We next used our own GeneChip and The Cancer Genome Atlas database to collect the possible target genes of MALAT1 and further utilized a bioinformatics analysis to explore the underlying significant pathways that might be crucial in PC. Finally, we identified several key target genes of MALAT1 and hope to offer references for future research. RESULTS: We found that the expression of MALAT1 was significantly elevated in patients with PC. A receiver operating characteristics curve analysis showed a moderate diagnostic value (area under the curve =0.75, sensitivity =0.66, specificity =0.72). A total of 224 important overlapping genes were collected, and six hub genes (CCND1, MAPK8, VEGFA, FOS, CDH1, and HSP90AA1) were identified, of which CCND1, MAPK8, and VEGFA, are important genes in PC. Several pathways, including the mTOR signaling pathway, pathways in cancer, and the MAPK signaling pathway, were suggested to be the vital MALAT1 pathways in PC. CONCLUSION: MALAT1 is suggested to be a promising diagnostic biomarker in PC. Six hub genes (CCND1, MAPK8, VEGFA, FOS, CDH1, and HSP90AA1), and specifically CCND1, MAPK8, and VEGFA, might be key MALAT1 target genes in PC. Due to their possible clinical significance in PC, several pathways, such as the mTOR signaling pathway, pathways in cancer, and the MAPK signaling pathway, are worthy of further study.

Clinical value of miR-452-5p expression in lung adenocarcinoma: A retrospective quantitative real-time polymerase chain reaction study and verification based on The Cancer Genome Atlas and Gene Expression Omnibus databases.

The role and mechanism of miR-452-5p in lung adenocarcinoma remain unclear. In this study, we performed a systematic study to investigate the clinical value of miR-452-5p expression in lung adenocarcinoma. The expression of miR-452-5p in 101 lung adenocarcinoma patients was detected by quantitative real-time polymerase chain reaction. The Cancer Genome Atlas and Gene Expression Omnibus databases were joined to verify the expression level of miR-452-5p in lung adenocarcinoma. Via several online prediction databases and bioinformatics software, pathway and network analyses of miR-452-5p target genes were performed to explore its prospective molecular mechanism. The expression of miR-452-5p in lung adenocarcinoma in house was significantly lower than that in adjacent tissues (p < 0.001). Additionally, the expression level of miR-452-5p was negatively correlated with several clinicopathological parameters including the tumor size (p = 0.014), lymph node metastasis (p = 0.032), and tumor-node-metastasis stage (p = 0.036). Data from The Cancer Genome Atlas also confirmed the low expression of miR-452 in lung adenocarcinoma (p < 0.001). Furthermore, reduced expression of miR-452-5p in lung adenocarcinoma (standard mean deviations = -0.393, 95% confidence interval: -0.774 to -0.011, p = 0.044) was validated by a meta-analysis. Five hub genes targeted by miR-452-5p, including SMAD family member 4, SMAD family member 2, cyclin-dependent kinase inhibitor 1B, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta, were significantly enriched in the cell-cycle pathway. In conclusion, low expression of miR-452-5p tends to play an essential role in lung adenocarcinoma. Bioinformatics analysis might be beneficial to reveal the potential mechanism of miR-452-5p in lung adenocarcinoma.

Identification of molecular targets for esophageal carcinoma diagnosis using miRNA-seq and RNA-seq data from The Cancer Genome Atlas: a study of 187 cases.

Esophageal carcinoma (ESCA) is one of the most common malignancies worldwide, and its pathogenesis is complex. In this study, we identified differentially expressed miRNAs (DEMs) and genes (DEGs) of ESCA from The Cancer Genome Atlas (TCGA) database. The diagnostic values of DEMs were determined by receiver operating characteristic (ROC) analyses and validated based on data from Gene Expression Omnibus (GEO). The top five DEMs with the best diagnostic values were selected, and their potential targets were predicted by various in silico methods. These target genes were then identified among the DEGs from TCGA. Furthermore, the overlapping genes were subjected to protein-protein interaction (PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The miRNA-transcription factor (TF) regulatory relations were determined using CircuitsDB and TransmiR. Finally, the regulatory networks of miRNA-TF and miRNA-gene were constructed and analyzed. A total of 136 DEMs and 3541 DEGs were identified in ESCA. The top five DEMs with the highest area under the receiver operating characteristic curve (AUC) values were miRNA-93 (0.953), miRNA-21 (0.928), miRNA-4746 (0.915), miRNA-196a-1 (0.906) and miRNA-196a-2 (0.906). The combined AUC of these five DEMs was 0.985. The KEGG analysis with 349 overlapping genes showed that the calcium signaling pathway and the neuroactive ligand-receptor interaction were the most relevant pathways. The regulatory networks of miRNA-TF and miRNA-gene, including 38 miRNA-TF and 560 miRNA-gene pairs, were successfully established. Our findings may provide new insights into the molecular mechanisms of ESCA pathogenesis. Future research will aim to explore the role of novel miRNAs in the pathogenesis and improve the early diagnosis of ESCA.

Clinical value of miR-145-5p in NSCLC and potential molecular mechanism exploration: A retrospective study based on GEO, qRT-PCR, and TCGA data.

MicroRNAs have been reported to be involved in various biological processes. Here, we performed a systematic analysis to explore the clinical value and potential molecular mechanism of miR-145-5p in non-small cell lung cancer. First, a meta-analysis was performed with eligible literature, followed by microRNA microarrays in the Gene Expression Omnibus database, to verify the diagnostic and prognostic values of miR-145-5p. A cohort of 125 clinical paired non-small cell lung cancer samples was next used to detect the level of miR-145-5p and to explore the relationship of miR-145-5p with clinicopathological parameters. The Cancer Genome Atlas database was additionally applied to investigate the role of miR-145-5p in non-small cell lung cancer. The potential targets of miR-145-5p were predicted using 12 online prediction databases to explore the prospective molecular mechanism of miR-145-5p in non-small cell lung cancer. The expression of miR-145-5p in non-small cell lung cancer was significantly lower than that in healthy tissues. And miR-145-5p tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma. Furthermore, the expression of miR-145-5p was closely associated with lymph node metastasis in non-small cell lung cancer. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched with enzyme-linked receptor protein signaling pathways, SH3 domain binding, cell leading edge, and adherens junction. The protein-protein interaction network showed that eight hub genes (SMAD4, SMAD2, IRS1, FOXO1, ERBB4, NRAS, ACTB, and ACTG1) might be the key target genes of miR-145-5p in non-small cell lung cancer. The information we obtained might offer new perspectives for clinical diagnosis and treatment for non-small cell lung cancer.