Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC). A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC. Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA–miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein–protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis. Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA–miRNA–mRNA network view.

Aberrant expression of microRNA-148a (miR-148a) has been reported in several types of malignancies. However, its expression and clinicopathological significance in hepatocellular carcinoma (HCC) has not been entirely clarified. Our objective was to investigate the clinicopathological contribution of the miR-148a expression in HCC formalin-fixed paraffin-embedded (FFPE) tissues. Eighty-nine HCC and their para-cancerous liver tissues were recruited. Total mRNA including miRNA was isolated and miR-148a expression was determined by using real time RT-qPCR. Furthermore, the relationship between the miR-148a level and clinicopathological features was explored. Significantly lower miR-148a expression in HCC tissues was observed than that in adjacent noncancerous hepatic tissues. miR-148a expression was also correlated to clinical TNM stage, metastasis, status of capsular infiltration and numbers of tumor nodes. Underexpression of miR-148a might be associated with HCC tumorigenesis and deterioration of HCC. miR-148a might act as a suppressor miRNA of HCC and it therefore has a potential role in prognosis of HCC patients.

Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins of NSCLC. In this study, we explored the effect of miR-542-5p in NSCLC with clinical samples and in vivo models and further explored the prospective function of miR-542-5p though bioinformatics methods. A total of 125 NSCLC tissue samples were collected, and the expression of miR-542-5p was detected by qRT-PCR. The relationship between miR-542-5p level and clinicopathological features was analyzed. The effect of miR-542-5p on survival time was also explored with K-M survival curves and Cox’s regression. The effect of miR-542-5p on the tumorigenesis of NSCLC was verified with a chick chorioallantoic membrane (CAM) model. The potential target genes were predicted by bioinformatics tools, and relevant pathways were analyzed by GO and KEGG. Several hub genes were validated by Proteinatlas. The expression of miR-542-5p was down-regulated in NSCLC tissues, and consistent results were also found in the subgroups of adenocarcinoma and squamous cell carcinoma. Down-regulation of miR-542-5p was found to be connected with advanced TNM stage, vascular invasion, lymphatic metastasis and EGFR. Survival analyses showed that patients with lower miR-542-5p levels had markedly poorer prognosis. Both tumor growth and angiogenesis were significantly suppressed by miR-542-5p mimic in the CAM model. The potential 457 target genes of miR-542-5p were enriched in several key cancer-related pathways, such as morphine addiction and the cAMP signaling pathway from KEGG. Interestingly, six genes (GABBR1, PDE4B, PDE4C, ADCY6, ADCY1 and GIPR) from the cAMP signaling pathway were confirmed to be overexpressed in NSCLCs tissues. This evidence suggests that miR-542-5p is a potential tumor-suppressed miRNA in NSCLC, which has the potential to act as a diagnostic and therapeutic target of NSCLC.

Previous studies have investigated the association between HOXA13 and non‑small cell lung cancer. However, the role of HOXA13 expression in the occurrence and progression of lung adenocarcinoma (LUAD) has not yet been investigated. In the present study, HOXA13‑related data mining of The Cancer Genome Atlas (TCGA), polymerase chain reaction (PCR) data from our cases and the case information in Oncomine was conducted for validation. The expression data of HOXA13 in lung cancer cell lines were also collected from the Cancer Cell Line Encyclopedia (CCLE) database for further verification. A comprehensive meta‑analysis of the expression of HOXA13 was also performed, integrating the data of TCGA, in‑house PCR and Oncomine. Genes that were co‑expressed with HOXA13 were subsequently identified through cBioPortal and Multi Experiment Matrix (MEM), and the potential role and mechanism of HOXA13 in LUAD was investigated. The expression value of HOXA13 in the LUAD group, which comprised 237 cases, was 3.74±2.694, significantly higher than its expression value in the non‑cancerous group (0.92±0.608, P<0.001). The pooled SMD for HOXA13 was 0.346 (95% CI, 0.052‑0.640; P=0.068; I2=51.3%; P=0.021), The meta‑analysis of diagnostic tests revealed that the area under the summary receiver operating characteristic curve (SROC) was 0.78 (95% CI, 0.75‑0.82). The results demonstrated that HOXA13 is highly expressed in LUAD. In addition to the studies on HOXA13 expression in tissues, the expression data of HOXA13 in lung cancer cell lines were also collected from the CCLE database for further verification of these conclusions. Genes that were co‑expressed with HOXA13 were identified for pathway analysis. The most enriched Gene Ontology terms in the genes co‑expressed with HOXA13 were positive regulation of transcription from RNA polymerase II promoter, signal transduction and positive regulation of GTPase activity in biological process; cytoplasm, integral component of membrane and plasma membrane in cellular component; and significantly involved in protein binding, transcription factor activity, sequence‑specific DNA binding and sequence‑specific DNA binding in molecular function. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these target genes were clearly involved in Pathways in cancer, Proteoglycans in cancer and cAMP signaling pathway. The hub genes obtained from the four protein‑protein interaction networks were associated with HOXA13. The results of the bioinformatics research in the present study revealed that HOXA13 may influence the expression of these hub genes in such a way as to promote the occurrence and development of LUAD. In conclusion, the expression of HOXA13 in patients with LUAD and its potential clinical value were analyzed comprehensively in the present study using data from a variety of sources. Through bioinformatics analysis, evidence that HOXA13 may promote the occurrence and development of LUAD was obtained.

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored thein vitroeffect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.