Approximately 500,000 new head and neck squamous cell carcinoma (HNSCC) cases are detected every year around the world, and its incidence ranks sixth among all cancer types globally. Among these cases, oral squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC) are HNSCC subtypes with high incidence rates, especially in China. The present study examines the association between the apolipoprotein L1 (APOL1) mRNA and protein expression and clinical parameters in HNSCC. The two most common types (oral and larynx) of HNSCC were selected for subgroup analyses. Immunohistochemistry (IHC) was used to detect APOL1 protein expression levels in HNSCC clinical specimens. It was demonstrated that APOL1 protein expression in 221 cases of HNSCC was higher compared with that in normal tissues. Consistent upregulation of APOL1 protein was also found in subgroups of OSCC and LSCC. Through mining the ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, microarrays and RNA sequencing data for HNSCC were retrieved, which were used to analyze APOL1 mRNA expression levels. The results showed that APOL1 expression was higher in both OSCC and LSCC subtypes, as well as in HNSCC, compared with that in non-cancerous squamous epithelium. The summary receiver operating characteristic analysis showed that APOL1 had potential as a diagnostic biomarker for HNSCC, OSCC and LSCC. Thus, upregulation of APOL1 may contribute to the tumorigenesis of HNSCC.

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.

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.

Long non-coding RNAs (lncRNAs) have a role in the occurrence and development of lung squamous cell carcinoma (LUSC). lncRNA γ-butyrobetaine hydroxylase 1 (BBOX1)-antisense 1 (AS1) may contribute to disease development. However, there are no studies on the role of BBOX1-AS1 in LUSC to date. In the present study, an in-house gene microarray analysis was performed to detect the differentially expressed lncRNAs and mRNAs between three pairs of LUSC and normal lung tissues. Only one lncRNA, BBOX1-AS1, was differentially expressed in the in-house microarray and The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and ArrayExpress databases. Reverse transcription-quantitative PCR (RT-qPCR) was then performed and the original RNA-sequencing data from the TCGA, GEO and ArrayExpress datasets were used to determine the expression and clinical value of BBOX1-AS1 in LUSC. In addition, a Cell Counting Kit-8 assay, cell cycle analysis and scratch assay were performed to explore whether BBOX1-AS1 expression affected the proliferation and migration of LUSC cells in vitro. The results of the RT-qPCR analysis and data obtained from the TCGA database, GEO datasets, in-house gene microarray and standard mean deviation analysis all supported the upregulated expression level of BBOX1-AS1 in LUSC. Furthermore, silencing of BBOX1-AS1 inhibited the proliferation and migration of LUSC cells according to in vitro assays. In addition, the cells were arrested in S-phase after knockdown of BBOX1-AS1. In conclusion, the expression level of BBOX1-AS1 was upregulated in LUSC tissues. BBOX1-AS1 may exert an oncogenic effect on LUSC by regulating various biological functions. However, additional functional experiments should be performed to verify the exact mechanism.

The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed. Differentially expressed genes identified following miR-124-3p transfection, the prospective target genes predicted in silico and the key genes of HCC obtained from Natural Language Processing (NLP) were integrated to obtain potential target genes of miR-124-3p in HCC. Relevant signaling pathways were assessed with protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Annotation Through Evolutionary Relationships (PANTHER) pathway enrichment analysis. miR-124-3p expression was significantly reduced in HCC tissues compared with expression in adjacent non-cancerous liver tissues. In HCC, miR-124-3p was demonstrated to be associated with clinical stage. The mean survival time of the low miR-124-3p expression group was reduced compared with that of the high expression group. A total of 132 genes overlapped from differentially expressed genes, miR-124-3p predicted target genes and NLP identified genes. PPI network construction revealed a total of 109 nodes and 386 edges, and 20 key genes were identified. The major enriched terms of three GO categories included regulation of cell proliferation, positive regulation of cellular biosynthetic processes, cell leading edge, cytosol and cell projection, protein kinase activity, transcription activator activity and enzyme binding. KEGG analysis revealed pancreatic cancer, prostate cancer and non-small cell lung cancer as the top three terms. Angiogenesis, the endothelial growth factor receptor signaling pathway and the fibroblast growth factor signaling pathway were identified as the most significant terms in the PANTHER pathway analysis. The present study confirmed that miR-124-3p acts as a tumor suppressor in HCC. miR-124-3p may target multiple genes, exerting its effect spatiotemporally, or in combination with a diverse range of processes in HCC. Functional characterization of miR-124-3p targets will offer novel insight into the molecular changes that occur in HCC progression.

To investigate the prospective roles and the clinicopathological application of microRNA-21-5p (miR-21-5p) in hepatocellular carcinoma (HCC), the present review is based on 24 studies and bioinformatics investigation. Firstly, HCC-associated miR-21-5p data were aggregated from literature databases and two public genomic data repositories, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Potential target genes of miR-21-5p in HCC were identified using TCGA and GEO, Natural Language Processing and 14 online software packages. The oncogenic roles of these target genes was probed for understanding using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Hub genes were further investigated by protein-protein interaction network (PPI) analysis. Comprehensive meta-analysis, including 10 microarrays from GEO datasets, 13 literature studies and TCGA-based RNA sequencing data, indicated a reliable diagnostic capacity of miR-21-5p [area under the curve (AUC), 0.887; sensitivity, 0.78% and specificity, 0.79%]. The healthy control group (AUC, 0.926; sensitivity, 0.87% and specificity, 0.82%) demonstrated high diagnostic capacity of miR-21-5p compared with the chronic hepatitis B infection group (AUC, 0.904; sensitivity, 0.75% and specificity, 0.84%). A total of 10 significant enrichment pathways were indicated by KEGG analysis, with cytokine-cytokine receptor interaction exhibiting the highest score. A total of 5 genes, hepatocyte growth factor, forkhead box O1 (FOXO1), thrombospondin 1, estrogen receptor 1 (ESR1) and C-X-C motif chemokine ligand 12 were selected from 39 overlapping genes, according to the PPI network. Target genes were assembled in GO terms associated with 'response to chemical stimulus', 'cell surface' and 'growth factor binding'. In particular, low expression of FOXO1 and ESR1 was associated with miR-21-5p expression. In conclusion, upregulated expression of miR-21-5p may be a functional regulator of the metabolism or apoptosis in HCC and a novel tumor marker for the early diagnosis of HCC.

Long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) has been previously reported to be involved in the tumorigenesis and progression of ovarian cancer and glioma. However, the function of HOXA11-AS in lung cancer remains unclear. Following the knockdown of HOXA11-AS in A549 cells, a microarray analysis was performed in order to detect the differences in microRNA (miRNA/miR) profiles. Subsequently, miR-642b-3p was selected for further analysis. Four miRNA target prediction algorithms were used to identify potential target genes of miR-642b-3p. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes, protein-protein interactions (PPIs) and network analysis, were performed to investigate the potential functions, pathways and networks of the target genes. Furthermore, the differential expression of miR-642b-3p and its target genes between normal lung and non-small cell lung cancer (NSCLC) tissues was verified using The Cancer Genome Atlas (TCGA) database. Six target genes [zinc finger protein 350, heterogeneous nuclear ribonucleoprotein U, high mobility group box 1, phosphodiesterase 4D (PDE4D), synaptotagmin binding cytoplasmic RNA interacting protein and basic helix-loop-helix family member B9] of miR-642b-3p were predicted using all 4 algorithms. It was revealed that miR-642b-3p was overexpressed in adenocarcinoma and squamous cell carcinoma tissues compared with non-cancerous lung tissues based on the TCGA database. From the 6 target genes, PDE4D was downregulated in lung adenocarcinoma and squamous cell carcinoma tissues, and a weak negative correlation between HOXA11-AS and PDE4D was identified. The area under the curve of PDE4D was 0.905 [95% confidence interval (CI), 0.879-0.931] for patients with lung adenocarcinoma and 0.665 (95% CI, 0.606-0.725) for patients with squamous cell carcinoma. Additionally, GO analysis of the target genes revealed that miR-642b-3p was specifically involved in complex cellular pathways. The target gene RAN binding protein 2 possessed the highest degree of interactions in the PPI network (degree=40). It was hypothesized that HOXA11-AS may have a function in NSCLC by regulating the expression of miR-642b-3p and PDE4D, which laid the foundation for the further elucidation of the potential molecular mechanisms of NSCLC.