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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. [ABSTRACT FROM AUTHOR]

Exportin 1 (XPO1) is overexpressed in several solid tumors, and is associated with poor prognosis. Here, we aimed to evaluate the implication of XPO1 expression in solid tumors through a meta-analysis. PubMed, Web of Science, and Embase databases were searched for articles published until February 2023. Statistical data of the patients, odds ratios and hazard ratios (HRs), together with their corresponding 95% confidence intervals (CIs) were pooled to assess clinicopathological features and survival outcomes. Besides, the Cancer Genome Atlas (TCGA) was used to explore the prognostic significance of XPO1 in solid tumors. A total of 22 works, comprising 2595 patients were included in this study. The results suggested that increased XPO1 expression was associated with a higher tumor grade, more lymph node metastasis, advanced tumor stage, and progressively worse total clinical stage. Additionally, high XPO1 expression was associated with worse overall survival (OS) (HR = 1.43, 95% CI = 1.12–1.81, P = 0.004) and shorter progression-free survival (HR = 1.40, 95% CI = 1.07–1.84, P = 0.01). An analysis using the TCGA dataset showed that high XPO1 expression was associated with poor OS and disease-free survival. XPO1 is a promising prognostic biomarker and may constitute a therapeutic target for solid tumors. PROSPERO registration number: CRD42023399159 [ABSTRACT FROM AUTHOR]

Background. 4-Methoxydalbergione (4MOD) is a flavonoid isolated from the heartwood of Dalbergia. Studies have demonstrated that 4MOD exerts anticancer activities on bladder cancer and astrocytoma. However, the anticancer activity of 4MOD in hepatocellular carcinoma (HCC) remains unknown. This study aims to examine its anticancer activities and mechanisms in human liver cancer cells. Methods. CCK-8, colony forming, wound healing, transwell migration, and AnnexinV/PI assays were used to assess the anticancer effects of 4MOD in HCC cells. RNA sequencing (RNA-Seq) was selected to explore the possible mechanisms underlying the anti-HCC activity of 4MOD. The mRNA expression levels of target genes were verified through quantitative real-time PCR (qRT-PCR). A lentiviral shRNA interference technique was used to silence GADD45G expression. GADD45G knockdown was employed to confirm the crucial role of GADD45G in the 4MOD-mediatedanti-HCC effects. Results. 4MOD inhibited HCC cells' proliferation and migration and promoted tumor cell apoptosis. RNA-Seq and qRT-PCR analyses revealed that 4MOD treatment increased GADD45G expression. Silencing GADD45G reversed 4MOD-mediated inhibition of proliferation, migration, and promotion of apoptosis. Conclusions. Our findings show that 4MOD elicits anti-HCC effects by upregulating GADD45G expression and could be a valuable anticancer agent for liver cancer. [ABSTRACT FROM AUTHOR]

Cyclin‐dependent kinase 1 (CDK1) plays a significant role in certain malignancies. However, it remains unclear whether CDK1 plays a role in esophageal squamous cell carcinoma (ESCC). The aim of this study was to analyze the expression and clinical value of CDK1 in ESCC. CDK1 protein in 151 ESCC tissues and 138 normal esophageal tissues was detected by immunohistochemistry. RNA‐seq of eight pairs of ESCC and adjacent esophageal specimens was performed to evaluate the levels of CDK1 mRNA. Microarray and external RNA‐seq data from 664 cases of ESCC and 1733 cases of control tissues were used to verify the difference in CDK1 expression between the two groups. A comprehensive analysis of all data was performed to evaluate the difference in CDK1 between ESCC tissues and control tissues. Further, functional enrichment analyses were performed based on differentially expressed genes (DEGs) of ESCC and co‐expressed genes (CEGs) of CDK1. In addition, a lncRNA‐miRNA‐CDK1 network was constructed. The expression of CDK1 protein was obviously increased in ESCC tissues (3.540 ± 2.923 vs. 1.040 ± 1.632, P < 0.001). RNA‐seq indicated that the mRNA level of CDK1 was also highly expressed in ESCC tissues (5.261 ± 0.703 vs. 2.229 ± 1.161, P < 0.0001). Comprehensive analysis revealed consistent up‐regulation of CDK1 (SMD = 1.41; 95% CI 1.00–1.83). Further, functional enrichment analyses revealed that the functions of these genes were mainly concentrated in the cell cycle. A triple regulatory network of PVT1‐hsa‐miR‐145‐5p/hsa‐miR‐30c‐5p‐CDK1 was constructed using in silico analysis. In summary, overexpression of CDK1 is closely related to ESCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC).Methods: Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references.Results: The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation.Conclusions: The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p. [ABSTRACT FROM AUTHOR]

BACKGROUND: The expression of neuropilin-1 (NRP-1) in Epstein-Barr virus (EBV)-associated lymphomas and its relationships with clinicopathological parameters was investigated. METHODS: The researchers compared 111 cases of patients with lymphoma to 20 cases of reactive lymphoid hyperplasia. In situ hybridization was applied to observe the expression of EBV-encoded RNA (EBER) in lymphomas, and immunohistochemistry was used to detect the NRP-1 expression in lymphoma tissues and lymph node tissues with reactive hyperplasia. RESULTS: In these 111 cases, the EBER of 62 cases (55.9%) appeared positive. NRP-1 was relatively highly expressed in lymphomas (P = 0.019). Further, NRP-1 showed higher expression in lymphomas with positive EBER than in negative ones. A comprehensive analysis revealed that NRP-1 was differently expressed in NK/T-cell lymphoma, Hodgkin's lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma (P = 0.027). Moreover, highly expressed NRP-1 was found to be a useful independent prognostic factor in assessing overall survival and progression-free survival rates in cases of non-Hodgkin's lymphoma (NHL). CONCLUSIONS: NRP-1 exhibited higher expression in lymphomas, and it was positively expressed in EBV-positive lymphomas. Moreover, highly expressed NRP-1 can be used as an undesirable independent prognostic factor in NHL. [ABSTRACT FROM AUTHOR]

miR-15b-5p has frequently been reported to function as a biomarker in some malignancies; however, the function of miR-15b-5p in hepatocellular carcinoma (HCC) and its molecular mechanism are still not well understood. The present study was designed to confirm the clinical value of miR-15b-5p and further explore its underlying molecular mechanism. A comprehensive investigation of the clinical value of miR-15b-5p in HCC was investigated by data mining The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets as well as literature. In addition, intersected target genes of miR-15b-5p were predicted using the miRWalk database and differentially expressed genes of HCC from TCGA. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. Then, a protein-protein interaction network (PPI) was constructed to reveal the interactions between some hub target genes of miR-15b-5p. The miR-15b-5p expression level in HCC was predominantly overexpressed compared with non-HCC tissues samples (SMD=0.618, 95% CI: 0.207, 1.029; P<0.0001) based on 991 HCC and 456 adjacent non-HCC tissue samples. The pooled summary receiver operator characteristic (SROC) of miR-15b-5p was 0.81 (Q*=0.74), and the pooled sensitivity and specificity of miR-15b-5p in HCC were 72% (95% CI: 69–75%) and 68% (95% CI: 65–72%), respectively. Bioinformatically, 225 overlapping genes were selected as prospective target genes of miR-15b-5p in HCC, and profoundly enriched GO terms and KEGG pathway investigation in silico demonstrated that the target genes were associated with prostate cancer, proximal tubule bicarbonate reclamation, heart trabecula formation, extracellular space, and interleukin-1 receptor activity. Five genes (ACACB, RIPK4, MAP2K1, TLR4 and IGF1) were defined as hub genes from the PPI network. The high expression of miR-15b-5p could play an essential part in hepatocarcinogenesis through diverse regulation approaches. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinoma (GAC) is a challenging disease with dim prognosis even after surgery; hence, novel treatments for GAC are in urgent need. The aim of the present study was to explore new potential compounds interfering with the key pathways related to GAC progression. The differentially expressed genes (DEGs) between GAC and adjacent tissues were identified from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Connectivity Map (CMap) was performed to screen candidate compounds for treating GAC. Subsequently, pathways affected by compounds were overlapped with those enriched by the DEGs to further identify compounds which had anti-GAC potential. A total of 843 DEGs of GAC were identified. Via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 13 pathways were significantly enriched. Moreover, 78 compounds with markedly negative correlations with DEGs were revealed in CMap database (P<0.05 and Enrichment <0). Subpathways of cell cycle and p53 signaling pathways, and core genes of these compounds, cyclin B1 (CCNB1) and CDC6, were identified. This study further revealed seven compounds that may be effective against GAC; in particular methylbenzethonium chloride and alexidine have never yet been reported for GAC treatment. In brief, the candidate drugs identified in this study may provide new options to improve the treatment of patients with GAC. However, the biological effects of these drugs need further investigation. [ABSTRACT FROM AUTHOR]

A combination of a Wilms' tumor (WT) and renal cell carcinoma (RCC) is an extremely rare pediatric renal neoplasm. Its prognosis and clinicopathological features remain unclarified. Herein, we describe a case of the coexistence of a WT and an RCC in a male child aged 5 years and 10 months. The child had symptoms of hematuria for more than 1 month. Although his irises were clear, medical imaging revealed a potential malignant tumor in the left kidney. The patient underwent resection of the left kidney. The pathological diagnosis was the coexistence of a WT and papillary RCC. Negative surgical margins were examined. One month following the resection, chemotherapy with vincristine plus dactinomycin (EE-4A regimen) was commenced. At the 69-month follow-up, there was no recurrence or metastasis. The coexistence of a WT and an RCC in the pediatric population is considered a rare pathological event. At present, there is no standard treatment for these renal neoplasms. In this study, the RCC treatment, which was the same as that applied in cases of WTs, was reasonable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aims of the present study were to examine the potential role of microRNA-233-3p (miR)-223-3p in the tumorigenesis of hepatocellular carcinoma (HCC), and to investigate its diagnostic accuracy and potential molecular mechanisms. The expression data of miR-223-3p in HCC were obtained from the Gene Expression Omnibus (GEO). Data for the precursor miR-223 were obtained from The Cancer Genome Atlas (TCGA). The diagnostic role of miR-223-3p was identified by the receiver operating curve (ROC), and the diagnostic value of miR-223-3p in HCC was calculated from qualified reports in the literature. In addition, associated data from the GEO, TCGA and qualified experiments were pooled for comprehensive meta-analysis. Genes, which intersected between online prediction databases, natural language processing and differentially expressed genes from TCGA were regarded as potential targets of miR-223-3p in HCC. The Gene Ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathways of potential targets were performed using the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interactions were mapped using the Search Tool for the Retrieval of Interacting Genes. Among 15 qualified microarray data sets from GEO, seven showed that a significantly lower level of miR-223-3p was present in the HCC tissues, compared with that in non-cancerous tissues (P<0.05). In addition, five GEO data sets revealed diagnostic values of miR-223-3p, with an area under the curve (AUC) of >0.80 (P<0.05). The diagnostic accuracy of the precursor miR-223 in TCGA was also calculated (AUC=0.78, P<0.05). Similarly, the precursor miR-223 showed a higher level of downregulation in HCC tissues, compared with that in healthy controls in TCGA (P<0.001). A summary ROC was also calculated as 0.89 (95% CI, 0.85-0.91) in the meta-analysis. A total of 72 potential targets were extracted, mainly involved in the terms 'microRNAs in cancer', 'ATP binding' and 'prostate cancer'. Five potential target genes were considered the hub genes of miR-223-3p in HCC, including checkpoint kinase 1, DNA methyltransferase 1, baculoviral IAP repeat containing 5, kinesin family member 23, and collagen, type I, a1. Based on TCGA, the hub genes were significantly upregulated in HCC (P<0.05). Collectively, these results showed that miR-223-3p may be crucial in HCC carcinogenesis showing high diagnostic accuracy, and may be mediated by several hub genes. [ABSTRACT FROM AUTHOR]

Background: Currently, some studies have demonstrated that miR-34a could serve as a suppressor of several cancers including hepatocellular carcinoma (HCC). Previously, we discovered that miR-34a was downregulated in HCC and involved in the tumorigenesis and progression of HCC; however, the mechanism remains unclear. The purpose of this study was to estimate the expression of miR-34a in HCC by applying the microarray profiles and analyzing the predicted targets of miR-34a and their related biological pathways of HCC.Methods: Gene expression omnibus (GEO) datasets were conducted to identify the difference of miR-34a expression between HCC and corresponding normal tissues and to explore its relationship with HCC clinicopathologic features. The natural language processing (NLP), gene ontology (GO), pathway and network analyses were performed to analyze the genes associated with the carcinogenesis and progression of HCC and the targets of miR-34a predicted in silico. In addition, the integrative analysis was performed to explore the targets of miR-34a which were also relevant to HCC.Results: The analysis of GEO datasets demonstrated that miR-34a was downregulated in HCC tissues, and no heterogeneity was observed (Std. Mean Difference(SMD) = 0.63, 95% confidence intervals(95%CI):[0.38, 0.88], P < 0.00001; Pheterogeneity = 0.08 I2 = 41%). However, no association was found between the expression value of miR-34a and any clinicopathologic characteristics. In the NLP analysis of HCC, we obtained 25 significant HCC-associated signaling pathways. Besides, we explored 1000 miR-34a-related genes and 5 significant signaling pathways in which CCND1 and Bcl-2 served as necessary hub genes. In the integrative analysis, we found 61 hub genes and 5 significant pathways, including cell cycle, cytokine-cytokine receptor interaction, notching pathway, p53 pathway and focal adhesion, which proposed the relevant functions of miR-34a in HCC.Conclusion: Our results may lead researchers to understand the molecular mechanism of miR-34a in the diagnosis, prognosis and therapy of HCC. Therefore, the interaction between miR-34a and its targets may promise better prediction and treatment for HCC. And the experiments in vivo and vitro will be conducted by our group to identify the specific mechanism of miR-34a in the progress and deterioration of HCC. [ABSTRACT FROM AUTHOR]

Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR- 224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224- 5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224- 5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification. [ABSTRACT FROM AUTHOR]

Abstract Background Although previous researchers have analyzed the expression level of vimentin in nasopharyngeal carcinoma (NPC), the sample size of each study was too small, and there was no further in-depth study utilizing microarray and RNA-sequencing data. More importantly, the role and molecular mechanism of vimentin in NPC have not yet been addressed comprehensively. Accordingly, the aim of the present research was to conduct a full exploration of the clinical significance of vimentin in NPC in a large sample size. Materials and methods Immunohistochemistry was used to test the expression of vimentin in clinical samples. Data from relevant microarray and RNA-sequencing datasets were screened and extracted to explore the clinical role of vimentin in NPC. Subsequently, vimentin-related signaling pathways were investigated via in-silico approaches. Results The clinical immunohistochemistry detection showed the positive expression ratio of vimentin was 24.6% (14/57) of the NPC specimens, whereas vimentin expression was negative in nasopharyngitis (NPG) tissues (0/20, P = 0.016). The mRNA and protein levels of vimentin were both remarkably up-regulated in NPC based on 196 and 1566 cases, respectively. The protein level of vimentin was also a risky factor for the prognosis prediction of NPC with the hazard ratios (HR) being 3.831. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses, the localization of vimentin was in both the cytoplasm and the cytoskeleton, and vimentin was involved in the regulation of molecular function, the execution phase of apoptosis, and the regulation of cellular component organization. Conclusion The high expression of vimentin plays a pivotal role in the development and poor progression of NPC, which indicates that vimentin may be an effective predictive indicator for NPC. [ABSTRACT FROM AUTHOR]

Abstract Malignant tumors of the digestive tract include esophageal, gastric, and colorectal carcinomas, which all have high global mortality rates. A clinical role for small nuclear RNA (snRNA), a type of small non-coding RNA, has not yet been documented for digestive tract pan-adenocarcinomas. Therefore, the aim of the study was to identify differentially expressed snRNAs and to explore their prognostic implications in pan-adenocarcinomas from the esophagus, stomach, colon, and rectum. The pan-carcinoma RNA-sequencing data of four types of digestive tract cancers with 1, 102 cases obtained from The Cancer Genome Atlas (TCGA) project were analyzed and the differentially expressed snRNAs were evaluated using the edgeR package. The prognostic value of each of the selected snRNAs was determined by univariate and multivariate Cox regression analyses. All the digestive tract pan-adenocarcinomas showed differential expression of three snRNAs: the up-regulated RNU1-106 P and RNU6-850 P and the down-regulated RNU6-529 P. Interestingly, RNU6-101 P appeared to be a risk factor for esophageal adenocarcinoma (ESAD) and RNVU1-4 was potentially a protective factor for stomach adenocarcinoma (STAD) survival. This consistent finding of differential expression of all three snRNAs in all four types of digestive system cancers suggests potential roles for these snRNAs in the tumorigenesis of digestive system cancers. RNU6-101 P could play a pivotal role in the progression of ESAD and RNVU1-4 could perform a protective role in STAD. However, since the current findings were based on RNA-sequencing data mining, more studies are needed for verification. [ABSTRACT FROM AUTHOR]

Objective To investigate the pathological features of fatal pediatric hand foot and mouth disease (HFMD). Methods The histopathological features of HFMD were first summarized from literature, and then confirmed by in-house autopsies. Furthermore, immunohistochemistry was conducted to detect the distribution and expression level of two enterovirus 71 (EV71) receptors scavenger receptor class B, member 2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL1) in the samples of autopsies. Results The main symptoms of HFMD included hand and foot rashes, as well as oral herpes. The fatal HFMD patients had typical histopathological change in the central nervous system, such as encephaledema and encephalitis. As for respiratory system, the fatal HFMD patients suffered acute pulmonary edema and congestion. SCARB2 positive signaling was distributed equally in bronchial and bronchiolar epithelial cells, alveolar epithelial cells and inflammatory cells of all HFMD patients, healthy children and adults without significant difference. PSGL-1 dispersed in bronchial and bronchiolar epithelial cells of healthy adults, but no PSGL-1 expression was detected in HFMD patients and healthy children. Conclusions Both of the central nervous and respiratory systems may be involved in the fatal HFMD patients. The EV71 receptor PSGL-1 might play essential parts in the pathogenesis of fatal HFMD, however, the hypothesis needs to be further investigated. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cancer worldwide. However, the expression and potential mechanism of miR-375 in BC are still controversial. We first collected microRNA chips and microRNA sequencing data from multiple databases for analyzing the expression level of miR-375, and further exploring the target genes and underlying molecular mechanism in BC. miR-375 in BC was predominantly overexpressed compared with that in normal breast tissues (pooled standard mean difference [SMD] = 0.49; 95 % confidence interval [CI]: 0.24–0.73, p < 0.0001). Meanwhile, the overall pooled area under the curve (AUC) in the summary receiver operating characteristic (SROC) of miR-375 was 0.83 (95 % CI = 0.79–0.86) based on 2928 cases of BC patients and 816 cases of controls, while the diagnostic positive likelihood ratio (DLR) positive and the DLR negative value were 3.90 (95 % CI = 2.46–6.19) and 0.39 (95 % CI = 0.28–0.54), respectively. The hazard ratios (HRs) were 1.29 (95 % CI = 1.04–1.6, P = 0.02) and 1.23 (95 % CI = 0.89–1.7, P = 0.22) for the cohorts of METABRIC and The Cancer Genome Atlas (TCGA). In vitro study demonstrated that miR-375 inhibitor could suppress the cell growth and induce apoptosis of BC cells. A total of 107 overlapping genes from microarrays after miR-375 transfection, the TCGA RNA sequencing, the microarrays of Affymetrix platform, and online predicting software were selected as the prospective targets of miR-375 in BC. Based on Gene Ontology (GO) enrichment analysis, the potential targets of miR-375 were notable for their somatic stem cell division, plasma membrane, and proline-rich region binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination demonstrated that the targets were associated with the pathways of prion diseases, proteoglycans in cancer, and focal adhesion. Then, 107 targets of miR-375 in BC were used to construct a protein–protein interaction (PPI) network. Finally, EGFR, PRKCA, PPARA, ADIPOQ, and ITSN1 were found to be the hub genes of miR-375. These targets showed negative correlations with miR-375 level. The upregulated miR-375 might play an essential part in the tumorigenesis and progression of BC. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to systematically appraise the clinicopathological significance and explore the molecular bases of CKS2 in endometrial carcinoma. Patients and Methods: We measured the clinicopathological significance of CKS2 using diverse methods of public RNA-seq, microarrays, and in-house tissue microarrays to investigate the molecular basis of CKS2 in endometrial carcinoma through upstream transcriptional analysis, immune infiltration correlation analysis, and co-expression analysis. Results: Both the analysis for public RNA-seq plus the microarray data and in-house tissue microarray confirmed the significant overexpression of CKS2 in a total of 1,021 endometrial carcinoma samples compared with 279 non-cancer endometrium samples (SMD = 2.10, 95% CI = 0.72-3.48). The upregulated CKS2 was significantly related to the lymph node metastasis and advanced clinical grade of endometrial carcinoma patients ( p < 0.001). Mutation types such as amplification and mRNA occurred with high frequency in the CKS2 gene in endometrial carcinoma patients. A series of miRNAs and transcription factors, such as hsa-miR-26a, hsa-miR-130a, hsa-miR-30, E2F4, MAX, and GABPA, were predicted to regulate the transcription and expression of CKS2. Significant links were found between CKS2 expression and the infiltration level of B cells, CD4 + T cells, and neutrophils in endometrial carcinoma. CKS2-coexpressed genes were actively involved in pathways such as the mitotic cell cycle process, PID aurora B pathway, and prolactin signaling pathway. Conclusion: The overexpressed CKS2 showed positive correlations with the clinical progression of endometrial carcinoma and was associated with various cancer-related biological processes and pathways, showing potential as a promising clinical biomarker for endometrial carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Chen, Liang, Li, Li, Tang, Tang, Huang, Chen, Luo, Zeng, Dang and Feng.)

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., Competing Interests: Gang Chen is an Academic Editor for PeerJ., (©2022 He et al.)

Background: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD., Methods: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments., Results: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells., Conclusions: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95%CI = 0.619-0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways.

Background: Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer., Methods: A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Immunohistochemistry was performed for evaluating PLK1 expression between cervical cancer (including cervical squamous cell carcinoma (CESC) and cervical adenocarcinoma) and non-cancer samples. The Expression Atlas database was searched for querying PLK1 expression in different cervical cancer cell lines and different tissues in the context of pan-cancer. Standard mean difference (SMD) was calculated and the summarized receiver's operating characteristics (SROC) curves were plotted for integrated tissue microarrays, exterior high-throughput microarrays and RNA sequencing data as further verification. The effect of PLK1 expression on the overall survival, disease-free survival and event-free survival of cervical cancer patients was analyzed through Kaplan Meier survival curves for cervical cancer patients from RNA-seq and GSE44001 datasets. The gene mutation and alteration status of PLK1 in cervical cancer was inspected in COSMIC and cBioPortal databases. Functional enrichment analysis was performed for genes correlated with PLK1 from aggregated RNA-seq and microarrays., Results: A total of 963 cervical cancer samples and 178 non-cancer samples were collected from in-house tissue microarrays and exterior microarrays and RNA-seq datasets. The combined expression analysis supported overexpression of PLK1 in CESC, cervical adenocarcinoma and all types of cervical cancer (SMD = 1.59, 95%CI [0.56-2.63]; SMD = 2.99, 95%CI [0.75-5.24]; SMD = 1.57, 95% CI [0.85-2.29]) and the significant power of PLK1 expression in distinguishing CESC or all types of cervical cancer samples from non-cancer samples (AUC = 0.94, AUC = 0.92). Kaplan-Meier survival curves showed that the event-free survival rate of cervical cancer patients with higher expression of PLK1 was shorter than that of patients with lower PLK1 (HR = 2.020, P  = 0.0197). Genetic alteration of PLK1 including missense mutation and mRNA low occurred in 6% of cervical cancer samples profiled in mRNA expression. Genes positively or negatively correlated with PLK1 were mainly assembled in pathways such as DNA replication, cell cycle, mismatch repair, Ras signaling pathway, melanoma, EGFR tyrosine kinase inhibitor resistance and homologous recombination ( P  < 0.05)., Conclusions: Here, we provided sufficient evidence of PLK1 overexpression in cervical cancer. The overexpression of PLK1 in cervical cancer and the contributory effect of it on clinical progression indicated the hopeful prospect of PLK1 as a biomarker for cervical cancer., Competing Interests: The authors declare there are no competing interests., (©2020 Gao et al.)

RNA molecules and targeting microRNA (miRNA) have been reported as novel focuses in recent research on breast cancer. This study aimed to probe the expression of FOXO1 in the MDA-MB-231 cell line and to explore the target effects of FOXO1 with hsa-microRNA-204-5p (miR-204) on the biologic behavior of MDA-MB-231 cells. The expression of FOXO1 mRNA and protein in MDA-MB-231 cells were derived and verified from the public databases, literature, and experimental assays, then the downregulation of FOXO1 was confirmed in the MDA-MB-231 cell line. The target binding of FOXO1 and miR-204 was predicted by miRWalk and confirmed by luciferase reporter assays. MiR-204 targeted the 3' untranslated region of FOXO1 and reduced FOXO1 expression in miR-204-transfected cells, resulting in cell growth amplification but inhibition of cell migration and apoptosis, which were assessed using the MTT method, wound healing assays, and flow cytometry, respectively. The protein levels of serine-threonine kinase (AKT), c-jun N-terminal kinase (JNK), extracellular regulatory protein kinase (ERK), and the phosphorylated protein kinases (P-AKT, P-JNK, and P-ERK) were measured by western blot. It was found that AKT, JNK, and ERK remained constant, but P-AKT, P-JNK, and P-ERK were upregulated after miR-204 transfection. In summary, the expression of FOXO1 was downregulated in MDA-MB-231 cells; and the target binding of miR-204 and FOXO1 affected phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signal pathways, leading to different alterations of cellular activity in MDA-MB-231 cells., Competing Interests: None., (IJCEP Copyright © 2020.)

Background: Hepatocellular carcinoma (HCC) is the second-highest cause of malignancy-related death worldwide, and many physiological and pathological processes, including cancer, are regulated by microRNAs (miRNAs). miR-193a-3p is an anti-oncogene that plays an important part in health and disease biology by interacting with specific targets and signals., Methods: In vitro assays were performed to explore the influences of miR-193a-3p on the propagation and apoptosis of HCC cells. The sequencing data for HCC were obtained from The Cancer Genome Atlas (TCGA), and the expression levels of miR-193a-3p in HCC and non-HCC tissues were calculated. The differential expression of miR-193a-3p in HCC was presented as standardized mean difference (SMD) with 95% confidence intervals (CIs) in Stata SE. The impact of miR-193a-3p on the prognoses of HCC patients was determined by survival analysis. The potential targets of miR-193a-3p were then predicted using miRWalk 2.0 and subjected to enrichment analyses, including Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Protein-Protein Interaction (PPI) network analysis. The interaction between miR-193a-3p and one predicted target, Cyclin D1 (CCND1), was verified by dual luciferase reporter assays and Pearson correlation analysis., Results: MiR-193a-3p inhibited the propagation and facilitated the apoptosis of HCC cells in vitro . The pooled SMD indicated that miR-193a-3p had a low level of expression in HCC (SMD: -0.88, 95% CI [-2.36 -0.59]). Also, HCC patients with a higher level of miR-193a-3p expression tended to have a favorable overall survival (OS: HR = 0.7, 95% CI [0.43-1.13], P  = 0.14). For the KEGG pathway analysis, the most related pathway was "proteoglycans in cancer", while the most enriched GO term was "protein binding". The dual luciferase reporter assays demonstrated the direct interaction between miR-193a-3p and CCND1, and the Pearson correlation analysis suggested that miR-193a-3p was negatively correlated with CCND1 in HCC tissues ( R  =  - 0.154, P  = 0.002)., Conclusion: miR-193a-3p could suppress proliferation and promote apoptosis by targeting CCND1 in HCC cells. Further, miR-193a-3p can be used as a promising biomarker for the diagnosis and treatment of HCC in the future., Competing Interests: The authors declare there are no competing interests., (©2020 Wang et al.)

Objective : To enquire into the clinical significance and potential molecular mechanism of microRNA (miRNA)-196b-5p in hepatocellular carcinoma (HCC). Methods : Quantitative reverse transcription and polymerase chain reaction (qRT-PCR) were utilized to examine miR-196b-5p expression level in 67 HCC paraffin embedded tissues and corresponding adjacent tissues. Correlations of miR-196b-5p expression level with clinicopathological characteristics were analyzed in our study. The expression level and clinical significance of miR-196b-5p in HCC were also evaluated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We made predictions of the target genes of miR-196b-5p by twelve online software and then selected genes predicted by at least 5 software. Subsequently, in order to obtain the potential target genes of miR-196b-5p, we overlapped the predicted target genes and down-regulated mRNAs in HCC based on TCGA database. Then, we performed the Gene Ontology (GO) and the Disease Ontology (DO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein Interaction (PPI) network construction of those miR-196b-5p potential target genes. Results : Higher expression level of miR-196b-5p was seen in HCC tissues than in the corresponding adjacent tissues based on qRT-PCR ( P = 0.0007). The expression level of miR-196b-5p was linked with tumor size ( P = 0.03), tumor node ( P = 0.024), vascular invasion ( P = 0.029) and capsular invasion ( P = 0.026) in HCC patients. Comprehensive meta-analysis of miR-196b-5p expression based on TCGA, GEO and qRT-PCR verified that higher expression level of miR-196b-5p was observed in HCC tissues than in normal control liver tissues (SMD = 0.56, 95%CI: 0.39-0.72, P heterogeneity = 0.275, I 2 = 18.3%). GO annotation revealed that the top terms in biological process, cellular component and molecular function were single-organism catabolic process, neuronal cell body and transmembrane receptor protein kinase activity, respectively. The most relevant disease in DO annotation was arteriosclerosis. The tryptophan metabolism pathway ranked first in KEGG pathway enrichment analysis. The PPI network showed that IGF1, FOXO1, AR and FOS were mostly likely to become the core genes of miR-196b-5p potential target genes, which however required further experiments for validation. Conclusion : The miR-196b-5p was observed to show higher expression in HCC tissues than in normal control liver tissues. Moreover, the miR-196b-5p expression level had correlations with the clinicopathological parameters such as vascular invasion of HCC, but the molecular mechanisms of miR-196b-5p in HCC still need further elucidation and verification., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Breast cancer (BC) is a kind of malignant cancer that seriously threatens women's health. Research scientists have found that BC occurs as the result of multiple effects of the external environment and internal genetic changes. Cell cycle checkpoint kinase 1 (CHEK1) is a crucial speed limit point in the cell cycle. Alterations of CHEK1 have been found in various tumors but are rarely reported or verified in BC. By mining database information, a large amount of mRNA and protein data was collected and meta-analyzed. Also, in-house immunohistochemistry was carried out to validate the results of the CHEK1 expression levels. Relative clinical features of BC patients were calculated with the CHEK1 expression levels to determine their diagnostic value. The mRNA levels of CHEK1 were higher in 1,089 cases of BC tissues than in 291 cases of non-BC tissues. We observed that the mRNA levels of CHEK1 are related to the clinical stages of BC patients (P = 0.008) and are also significant for overall survival (HR = 1.6, P = 0.0081). Using the immunohistochemistry method, we calculated and confirmed, using Fisher's exact test (P < 0.001), that a high-level CHEK1 protein is exhibited in BC tissues. Overexpressed CHEK1 mRNA promotes the occurrence of BC. Also, up-regulated CHEK1 could serve as an independent risk biomarker in BC patients' prognoses., Competing Interests: None., (IJCEP Copyright © 2019.)