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Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)-204-5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta-analysis that leveraged the standard mean difference (SMD) and summarized receiver operating characteristic (sROC) to evaluate the expression of the precursor miR-204 and mature miR-204-5p in BC. Additionally, an intersection of predicted genes, differentially expressed genes (DEGs) from the TCGA database and the GEO database were plotted to acquire desirable putative genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses were performed to assess the potential pathways and hub genes of miR-204-5p in BC. A decreased trend in precursor miR-204 expression was detected in 1,077 BC tissue samples in comparison to 104 para-carcinoma tissue samples in the TCGA database. Further, the expression of mature miR-204-5p was markedly downregulated in 756 BC tissue samples in comparison to 76 para-carcinoma tissue samples in the UCSC Xena database. The outcome of the SMD from meta-analysis also indicated that the expression of miR-204-5p was markedly reduced in 2,306 BC tissue samples in comparison to 367 para-carcinoma tissue samples. Additionally, the ROC and sROC values indicated that miR-204-5p had a great discriminatory capacity for BC. In GO analysis, 'cell development', 'cell surface activity', and 'receptor agonist activity' were the most enriched terms; in KEGG analysis, 'endocytosis' was significantly enriched. Rac GTPase activating protein 1 (RACGAP1) was considered the hub gene in the PPI network. In conclusion, miR-204-5p may serve a suppressor role in the oncogenesis and advancement of BC, and miR-204-5p may have crucial functions in BC by targeting RACGAP1. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to explore the abnormal expression of dual-specificity protein phosphatase 1 (DUSP1) and its latent molecular mechanisms in ovarian carcinoma (OVCA). Materials and Methods: Two clinical cohorts collected from two different hospitals were used to evaluate the expression of DUSP1 protein in OVCA tissues. RNA-sequencing and microarray datasets were utilised to verify DUSP1 expression at mRNA levels in both OVCA tissues and in the peripheral blood of OVCA patients. Furthermore, an integrated calculation was performed to pool the standard mean difference (SMD) from each cohort in order to comprehensively assess the expression of DUSP1 in OVCA. Furthermore, we examined the relationship among DUSP1, tumour microenvironment (TME), and chemotherapy resistance in OVCA. Moreover, we used pathway enrichment analysis to explore the underlying mechanisms of DUSP1 in OVCA. Results: A pooled SMD of -1.19 (95% CI [-2.00, -0.38], p = 0.004) with 1,240 samples revealed that DUSP1 was downregulated in OVCA at both mRNA and protein levels. The area under the receiver operating characteristic curve of 0.9235 indicated the downregulated DUSP1 in peripheral blood may have a non-invasive diagnostic value in OVCA. Through six algorithms, we identified that DUSP1 may related to tumour-infiltrating T cells and cancer associated fibroblasts (CAFs) in OVCA. Pathway enrichment demonstrated that DUSP1 might participate in the mitogen-activated protein kinase (MAPK) signalling pathway. Furthermore, DUSP1 may have relations with chemotherapy resistance, and a favourable combining affinity was observed in the paclitaxel-DUSP1 docking model. Conclusion: DUSP1 was downregulated in OVCA, and this decreasing trend may affect the infiltration of CAFs. Finally, DUSP1 may have a targeting relation with paclitaxel and participate in MAPK signaling pathways., 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 Liang, He, Luo, Huang, Li, Zhong, Chen, Huang, Shi, Wei, Zeng, Zeng and Chen.)

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.)

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., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

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.)

Background: It is generally acknowledged that miRNAs play pivotal roles in the initiation and development of cancer. The aim of the current study is to investigate the clinicopathological role of miR-136-5p in lung adenocarcinoma and its underlying molecular mechanism., Materials and Methods: Data of a cohort of 1242 samples were provided by the Gene Expression Omnibus and The Cancer Genome Atlas to evaluate miR-136-5p expression in lung adenocarcinoma. A comprehensive meta-analysis integrating the expression data from all sources was performed, followed by a summary receiver operating curve plotted to appraise the upregulated expression of miR-136-5p in lung adenocarcinoma. Candidate targets of miR-136-5p were launched by the intersection of differentially expressed genes in The Cancer Genome Atlas and genes predicted by 12 web-based platforms. Then, hub genes were illustrated by a protein-protein interaction network. Furthermore, Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Protein Analysis Through Evolutionary Relationships analyses of potential target genes were carried out via bioinformatics tools., Results: MiR-136-5p expression was upregulated in lung adenocarcinoma versus normal tissues (standard mean difference = 0.43, 95% confidence interval: 0.27-0.58). The summary receiver operating characteristic curve further verified the upregulation of miR-136-5p in lung adenocarcinoma (area under curve = 0.7459). A total of 311 candidate target genes of miR-136-5p were gathered to create a protein-protein interaction network. Molecular mechanism analysis unveiled the potential miR-136-5p target genes participated in cell adhesion molecules, focal adhesion, complement and coagulation cascades and blood coagulation., Conclusion: MiR-136-5p is overexpressed in lung adenocarcinoma and is involved in the molecular mechanism of lung adenocarcinoma via suppressing the expressions of downstream targets, especially claudin-18, sialophorin and syndecan 2 that participate in cell adhesion., (Copyright © 2018. Published by Elsevier GmbH.)