Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. Previous studies have found that many microRNAs (miRNAs), including miRNA‑126‑3p, may play a critical role in the development of LUAD. However, no study of LUAD has researched the synergistic effects and co‑targets of both miRNA‑126‑3p and miRNA‑126‑5p. The present study used real‑time quantitative polymerase chain reaction (RT‑qPCR) to explore the expression values of miRNA‑126‑3p and miRNA‑126‑5p in 101 LUAD and 101 normal lung tissues. Ten relevant microarray datasets were screened to further validate the expression levels of miRNA‑126‑3p and ‑5p in LUAD. Twelve prediction tools were employed to obtain potential targets of miRNA‑126‑3p and miRNA‑126‑5p. The results showed that both miRNA‑126‑3p and ‑5p were expressed significantly lower in LUAD. A significant positive correlation was also present between miRNA‑126‑3p and ‑5p expression in LUAD. In addition, lower expression of miRNA‑126‑3p and ‑5p was indicative of vascular invasion, lymph node metastasis (LNM), and a later tumor/node/metastasis (TNM) stage of LUAD. The authors obtained 167 targets of miRNA‑126‑3p and 212 targets of miRNA‑126‑5p; 44 targets were co‑targets of both. Eight co‑target genes (IGF2BP1, TRPM8, DUSP4, SOX11, PLOD2, LIN28A, LIN28B and SLC7A11) were initially identified as key genes in LUAD. The results of the present study indicated that the co‑regulation of miRNA‑126‑3p and miRNA‑126‑5p plays a key role in the development of LUAD, which also suggests a fail‑proof mode between miRNA‑3p and miRNA‑126‑5p.

Papillary renal cell carcinoma (PRCC) accounts for 15‑20% of all kidney neoplasms and continually attracts attention due to the increase in the incidents in which it occurs. The molecular mechanism of PRCC remains unclear and the efficacy of drugs that treat PRCC lacks sufficient evidence in clinical trials. Therefore, it is necessary to investigate the underlying mechanism in the development of PRCC and identify additional potential anti‑PRCC drugs for its treatment. The differently expressed genes (DEGs) of PRCC were identified, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for functional annotation. Then, potential drugs for PRCC treatment were predicted by Connectivity Map (Cmap) based on DEGs. Furthermore, the latent function of query drugs in PRCC was explored by integrating drug‑target, drug‑pathway and drug‑protein interactions. In total, 627 genes were screened as DEGs, and these DEGs were annotated using KEGG pathway analyses and were clearly associated with the complement and coagulation cascades, amongst others. Then, 60 candidate drugs, as predicted based on DEGs, were obtained from the Cmap database. Vorinostat was considered as the most promising drug for detailed discussion. Following protein‑protein interaction (PPI) analysis and molecular docking, vorinostat was observed to interact with C3 and ANXN1 proteins, which are the upregulated hub genes and may serve as oncologic therapeutic targets in PRCC. Among the top 20 metabolic pathways, several significant pathways, such as complement and coagulation cascades and cell adhesion molecules, may greatly contribute to the development and progression of PRCC. Following the performance of the PPI network and molecular docking tests, vorinostat exhibited a considerable and promising application in PRCC treatment by targeting C3 and ANXN1.

Systemic treatment options for soft tissue sarcomas (STSs) have remained unchanged despite the need for novel drug candidates to improve STS outcomes. Drug repurposing involves the application of clinical drugs to different diseases, reducing development time, and cost. It has also become a fast and effective way to identify drug candidates. The present study used a computational method to screen three drug‑gene interaction databases for novel drug candidates for the treatment of several common STS histologic subtypes through drug repurposing. STS survival‑associated genes were generated by conducting a univariate cox regression analysis using The Cancer Genome Atlas survival data. These genes were then applied to three databases (the Connectivity Map, the Drug Gene Interaction Database and the L1000 Fireworks Display) to identify drug candidates for STS treatment. Additionally, pathway analysis and molecular docking were conducted to evaluate the molecular mechanisms of the candidate drug. Bepridil was identified as a potential candidate for several STS histologic subtype treatments by overlapping the screening results from three drug‑gene interaction databases. The pathway analysis with the Kyoto Encyclopedia of Genes and Genomes predicted that Bepridil may target CRK, fibroblast growth factor receptor 4 (FGFR4), laminin subunit β1 (LAMB1), phosphoinositide‑3‑kinase regulatory subunit 2 (PIK3R2), WNT5A, cluster of differentiation 47 (CD47), elastase, neutrophil expressed (ELANE), 15‑hydroxyprostaglandin dehydrogenase (HPGD) and protein kinase cβ (PRKCB) to suppress STS development. Further molecular docking simulation suggested a relatively stable binding selectivity between Bepridil and eight proteins (CRK, FGFR4, LAMB1, PIK3R2, CD47, ELANE, HPGD, and PRKCB). In conclusion, a computational method was used to identify Bepridil as a potential candidate for the treatment of several common STS histologic subtypes. Experimental validation of these in silico results is necessary before clinical translation can occur.

The downstream of tyrosine kinase 7 (DOK7) is an adaptor protein mediating signalling transduction between receptors and intracellular downstream molecules. Reduced expression of DOK7 has been observed in breast cancer. The present study aimed to investigate the role played by DOK7 in lung cancer. The expression of DOK7 at both mRNA and protein levels was evaluated in human lung cancer. A reduced expression of DOK7 transcripts was seen in lung cancers compared with normal lung tissues. Kaplan-Meier analyses showed that the reduced expression of DOK7 was associated with poorer overall survival and progression-free survival of patients with lung cancer. A further western blot analysis revealed a predominant expression of DOK7 isoform 1 (DOK7V1) in normal lung tissues, which was reduced in lung cancer. Forced overexpression of DOK7V1 in lung cancer cell lines, A549 and H3122 resulted in a decrease of in vitro cell proliferation and migration, while adhesion to extracellular matrix was enhanced following the expression. In conclusion, DOK7 was reduced in lung cancer and reduced DOK7 expression was associated with poorer survival. DOK7 isoform 1 plays an inhibitory role on the proliferation and migration of lung cancer cells in which Akt pathway may be involved.

Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α‑1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60‑1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84‑0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix‑receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.

Piwi‑interacting RNAs (piRNAs) comprise the largest class of non‑coding RNAs. They represent a molecular feature shared by all non‑aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non‑tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome‑wide significant and replicated cancer‑risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2‑fold change) expressed between the cases and controls, and 64.7% of the protein‑coding genes potentially regulated by the gastric cancer‑associated piRNAs were expressed in the human stomach. The expression of many cancer‑associated piRNAs was correlated with the genome‑wide and replicated cancer‑risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.

Non‑small‑cell lung cancer (NSCLC) is well established as one of the major subtypes of human lung cancer. NSCLC is characterized by a high incidence rate and poor patient prognosis. Previous studies have identified that long intergenic non-coding RNA (lincRNA) serves a key role in the development of tumor and malignant metastasis. However, the majority of the underlying mechanisms for lincRNA deregulation in various diseases, including cancer and diabetes, have not been completely elucidated. In the present study, the deregulation of lincRNA‑p21 in NSCLC tumor tissues in comparison to adjacent healthy tissues was examined using reverse transcription‑quantitative polymerase chain reaction. Furthermore, the effect of lincRNA‑p21 overexpression and knockdown on different NSCLC cell lines was further investigated in vitro. The association between lincRNA‑p21 expression and microRNA (miR)‑17‑5p level in NSCLC tumor cells was also investigated to clarify the underlying mechanism. The influence of miR‑17‑5p on different NSCLC cell lines A549 and PC9 were also examined in vitro using miR‑17‑5p mimics and inhibitors. Bioinformatics and luciferase assays were conducted to verify the direct binding sites on lincRNA‑p21 for miR‑17‑5p. The results demonstrated that there was a significant low‑expression of lincRNA‑p21 in NSCLC tumor tissues, and lincRNA‑p21 effectively inhibited the progression of lung cancer cells by suppressing cell proliferation and migration and promoting cell apoptosis. An evident negative association between lincRNA‑p21 and miR‑17‑5p expression was observed, and the inhibitory effect of overexpressed lincRNA‑p21 on lung cancer cells was counteracted by miR‑17‑5p. Bioinformatics and luciferase reporter analysis results confirmed that miR‑17‑5p is a direct target for lincRNA‑p21. The present study provides evidence for lincRNA‑p21 to inhibit the progression of NSCLC via direct targeting of a miR‑17‑5p associated signaling pathway.

The genome‑wide copy number analysis of circulating tumor cells (CTCs) provides a promising prognostic biomarker for survival in breast cancer liver metastasis (BCLM) patients. The present study aimed to confirm the prognostic value of the presence of CTCs in BCLM patients. We previously developed an assay for the genome‑wide pattern differences in copy number variations (CNVs) as an adjunct test for the routine imaging and histopathologic diagnosis methods to distinguish newly diagnosed liver metastases and recurrent liver metastases. Forty‑three breast cancer patients were selected for this study in which 23 newly diagnosed and 20 recurrent liver metastases were diagnosed by histopathology and 18F‑FDG PET/CT imaging. CTCs were counted from all patients using the CellSearch system and were confirmed by cytomorphology and three‑color immunocytochemistry. Genomic DNA of single CTCs was amplified using multiple annealing and looping based amplification cycles (MALBAC). Then, we compared the CTC numbers of newly diagnosed and recurrent BCLM patients using Illumina platforms. A high CTC frequency (>15 CTCs/7.5 ml blood) was found to be correlated with disease severity and metastatic progression, which suggests the value for CTCs in the diagnosis of BCLM in comparison with pathohistology and PET/CT imaging (P>0.05). Moreover, CTCs isolated from BCLM patients remained an independent prognostic detection factor associated with overall survival (P=0.0041). Comparison between newly diagnosed and recurrent liver metastases revealed different frequencies of CNVs (P>0.05). Notably, the CNV pattern of isolated CTCs of recurrent BCLM patients was similar to recurrent liver metastases (nearly 82% of the gain/loss regions). Functional enrichment analysis identified 25 genes as a CNV signature of BCLM. Among them, were defensin and β‑defensin genes, which are significantly associated with anti‑angiogenesis and immunomodulation signaling pathways. High CTC frequencies are effective in the evaluation and differentiation between newly diagnosed liver metastases from recurrent liver metastases. Future clinical studies will be necessary to fully determine the prognostic potential of CTC cluster signatures in patients with BCLM.

Paclitaxel (PXL) is a chemotherapeutic agent widely used in solid tumors. However, whether PXL causes premature ovarian insufficiency in women of reproductive age remains controversial. The aim of the present study was to answer how and for how long PXL affects fertility, and to identify the protective effect of gonadotropin‑releasing hormone agonist (GnRHa) in mice. A single dose of PXL was administered to 7‑week‑old female ICR mice. Mice were treated with GnRHa for 1 estrous cycle prior to chemotherapy, and for another following chemotherapy. On the days 1, 6, 11 and 16 following the administration of PXL, mice were assessed by ovarian histology, ovarian stimulation and mating experiment. Multiple doses of PXL were also administered to verify the duration of the gonadotoxicity of PXL. It was determined that PXL only destroyed antral follicles on day 1 following chemotherapy without reducing primordial follicles. In vitro experiments revealed that PXL impaired oocytes in metaphase, excluding those at the germinal vesicle stage. The number and quality of retrieved metaphaseⅡ(MⅡ) oocytes in PXL‑exposed mice were reduced on day 1 following chemotherapy, which was recovered on day 11. MⅡ oocytes from mice pretreated with GnRHa recovered on day 6 following chemotherapy. Following 3 estrous cycles in mice after the last dose of the 3‑dose paclitaxel administration, follicles in all stages and retrieved MII oocytes were recovered. It was concluded that the impairment caused by PXL on follicles and oocytes in mice lasted for <3 estrous cycles, which was shortened by pretreatment of GnRHa.

Cholangiocarcinoma (CCA) is one of the most common epithelial cell malignancies worldwide. However, its prognosis is poor. The aim of the present study was to examine the prognostic landscape and potential therapeutic targets for CCA. RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) dataset and processed. A total of 172 genes that were significantly associated with overall survival of patients with CCA were identified using the univariate Cox regression method. Bioinformatics tools were applied using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). It was identified that 'Wnt signaling pathway', 'cytoplasm' and 'AT DNA binding' were the three most significant GO categories of CCA survival-associated genes. 'Transcriptional misregulation in cancer' was the most significant pathway identified in the KEGG analysis. Using the Drug-Gene Interaction database, a drug-gene interaction network was constructed, and 31 identified genes were involved in it. The most meaningful potential therapeutic targets were selected via protein-protein and gene-drug interactions. Among these genes, polo-like kinase 1 (PLK1) was identified to be a potential target due to its significant upregulation in CCA. To rapidly find molecules that may affect these genes, the Connectivity Map was queried. A series of molecules were selected for their potential anti-CCA functions. 0297417-0002B and tribenoside exhibited the highest connection scores with PLK1 via molecular docking. These findings may offer novel insights into treatment and perspectives on the future innovative treatment of CCA.

The function of the expression of microRNA (miR)‑224‑5p in prostate adenocarcinoma (PCa) remains to be elucidated, therefore, the present study aimed to investigate the clinical significance and potential molecular mechanism of miR‑224‑5p in PCa. Data on the expression of miR‑224‑5p in PCa were extracted from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArrayExpress and previous literature, and meta‑analyses with standardized mean difference (SMD) and summary receiver operating characteristic (sROC) methods were performed for statistical analyses. The prospective target genes of miR‑224‑5p were collected by overlapping the differentially expressed mRNAs in TCGA and GEO, and target genes predicted by miRWalk2.0. Subsequently, in silico analysis was performed to examine the associated pathways of miR‑224‑5p in PCa. The expression of miR‑224‑5p was markedly lower in PCa; the overall SMD was ‑0.562, and overall sROC area under the curve was 0.80. In addition, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the prospective target genes of miR‑224‑5p were largely enriched in the amino sugar and nucleotide sugar metabolism signaling pathway, and three genes [UDP‑N‑acetylglucosamine pyrophosphorylase 1 (UAP1), hexokinase 2 (HK2) and chitinase 1 (CHIT1)] enriched in this pathway showed higher expression (P<0.05). In addition, key genes in the protein‑protein interaction network analysis [DNA topoisomerase 2‑α (TOP2A), ATP citrate lyase (ACLY) and ribonucleotide reductase regulatory subunit M2 (RRM2)] exhibited significantly increased expression (P<0.05). The results suggested that the downregulated expression of miR‑224‑5p may be associated with the clinical progression and prognosis of PCa. Furthermore, miR‑224‑5p likely exerts its effects by targeting genes, including UAP1, HK2, CHIT1, TOP2A, ACLY and RRM2. However, in vivo and in vitro experiments are required to confirm these findings.

Despite the fact that previous studies have reported the aberrant expression of miR‑183‑5p in lung adenocarcinoma (LUAD), the oncogenic role of miR‑183‑5p in LUAD and its underlying mechanisms have remained elusive. Hence, we attempted to elucidate the clinicopathological significance of miR‑183‑5p expression in LUAD and identify the biological function of miR‑183‑5p in LUAD in this study. Meta‑analysis of Gene Expression Omnibus (GEO) data, data mining of The Cancer Genome Atlas (TCGA) and real‑time quantitative polymerase chain reaction (qPCR) were performed to evaluate the clinicopathological significance of miR‑183‑5p in LUAD. Then, the effect of miR‑183‑5p on cell growth in LUAD was assessed by in vitro experiments. Additionally, the target genes of miR‑183‑5p were identified via miRWalk v.2.0 and TCGA. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Disease Ontology (DO) analysis were further carried out for the target genes. The targetability between target genes in key KEGG pathways and miR‑183‑5p was validated by independent samples t‑test, Pearson's correlation test and immunohistochemistry results from the Human Protein Atlas (HPA). According to the results, miR‑183‑5p was overexpressed in LUAD and exhibited significant diagnostic value. Moreover, miR‑183 expression was associated with tumor progression in the TCGA data. In vitro experiments revealed the positive influence of miR‑183‑5p on cell viability and proliferation as well as the negative effect of miR‑183‑5p on caspase‑3/7 activity in LUAD, which supports the finding that target genes of miR‑183‑5p are mainly enriched in gene pathways containing cell adhesion molecules (CAMs) and gene pathways important in cancer. Therefore, we conclude that miR‑183‑5p acts as an oncogene in LUAD and participates in the pathogenesis of LUAD via the interaction networks of its target genes.

The long non‑coding RNA (lncRNA) PVT1 plays vital roles in the tumorigenesis and development of various types of cancer. However, the potential expression profiling, functions and pathways of PVT1 in HCC remain unknown. PVT1 was knocked down in SMMC‑7721 cells, and a miRNA microarray analysis was performed to detect the differentially expressed miRNAs. Twelve target prediction algorithms were used to predict the underlying targets of these differentially expressed miRNAs. Bioinformatics analysis was performed to explore the underlying functions, pathways and networks of the targeted genes. Furthermore, the relationship between PVT1 and the clinical parameters in HCC was confirmed based on the original data in the TCGA database. Among the differentially expressed miRNAs, the top two upregulated and downregulated miRNAs were selected for further analysis based on the false discovery rate (FDR), fold‑change (FC) and P‑values. Based on the TCGA database, PVT1 was obviously highly expressed in HCC, and a statistically higher PVT1 expression was found for sex (male), ethnicity (Asian) and pathological grade (G3+G4) compared to the control groups (P<0.05). Furthermore, Gene Ontology (GO) analysis revealed that the target genes were involved in complex cellular pathways, such as the macromolecule biosynthetic process, compound metabolic process, and transcription. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the MAPK and Wnt signaling pathways may be correlated with the regulation of the four candidate miRNAs. The results therefore provide significant information on the differentially expressed miRNAs associated with PVT1 in HCC, and we hypothesized that PVT1 may play vital roles in HCC by regulating different miRNAs or target gene expression (particularly MAPK8) via the MAPK or Wnt signaling pathways. Thus, further investigation of the molecular mechanism of PVT1 in HCC is needed.

Nitidine chloride (NC), an inartificial bioactive alkaloid present in the root of Zanthoxylum nitidum (Roxb.) DC, is known for its versatile anti‑inflammation and anticancer capabilities. The molecular mechanisms underlying its anticancer properties, however, remain obscure. The authors of the present study demonstrated the tumor suppressive effects of NC in a human liver cancer cell line using an MTT assay. The tumor suppressive capacity of NC was also analysed in a tumor xenograft nude mouse model. Changes in tumor cell gene expression profiles following NC treatment were detected by microarray; bioinformatics analysis demonstrated that differentially expressed genes were enriched in several cancer‑associated pathways, including those initiated by transforming growth factor‑β and phosphatidylinositol 4,5‑bisphosphate 3‑kinase/RAC‑α serine/threonine‑protein kinase signaling. A Connectivity Map revealed that parthenolide, which has been identified previously as possessing anti‑inflammatory and anticancer functions, was potentially extremely similar in molecular function to NC. By screening the data from The Cancer Genome Atlas project, eight genes that were upregulated in liver cancer and significantly suppressed by NC treatment were identified. Overexpression of these genes was closely associated with advanced tumor stage and poor differentiation status. This combination of upregulated genes enabled successful identification and prediction of prognosis for liver cancer. The findings of the present study suggest that NC could inhibit the growth of liver cancer cells through several potential molecular targets and signaling pathways.

Patients with non‑muscle invasive bladder cancer (NMIBC) frequently relapse following surgery due to incomplete resection and chemoresistance, highlighting the importance of developing novel therapeutic strategies that mechanistically assist in eradicating the residual tumor. The aim of the present study was to evaluate the anticancer effect of chlorophyllin e6‑mediated photodynamic therapy (e6‑PDT) and its potential mechanisms by using monolayer cells or multicellular tumor spheroid models of human bladder cancer cells (T24 and 5637). The results revealed that e6‑PDT exhibited significant cytotoxicity in the T24 and 5637 cells of these two models as detected by the Water‑Soluble Tetrazolium Salts‑1 and CellTiter‑Glo Luminescent Cell Viability assays, respectively. Cell migration and invasion capacities decreased markedly following e6‑PDT. In addition, the cells following e6‑PDT exhibited typical morphological changes of apoptosis as detected by fluorescence microscopy with 4',6‑diamidino‑2‑phenylindole staining and transmission electron microscopy. A greater number of apoptotic cells were observed post‑e6‑PDT by flow cytometry. The expression levels of poly(adenosine diphosphate‑ribose) polymerase (PARP) and B‑cell lymphoma 2 protein were decreased, while cleaved PARP was increased, significantly following e6‑PDT as determined by western blotting. The level of intracellular reactive oxygen species (ROS) was increased, while the activity of superoxide dismutase (SOD) was decreased, significantly in e6‑PDT‑treated cells. Thus, the novel e6‑PDT exhibits prominent photo‑cytotoxicity effect and the induction of apoptosis was probably due to the inhibition of SOD activity and the generation of ROS. These results indicate that chlorophyllin e6 is an effective photosensitizer and that e6‑PDT may have a therapeutic application for the treatment of bladder cancer.

FK506 binding protein 10 (FKBP10) has been reported to be dysregulated in numerous types of cancer; however, few reports have investigated FKBP10 in gastric cancer (GC). The aim of the present study was to investigate FKBP10 expression in GC and to analyze its association with the prognosis of patients with GC. FKBP10 mRNA expression was evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The standardized mean differences of the meta‑analysis were comprehensively evaluated for FKBP10 expression from a series of GEO datasets. Kaplan‑Meier survival and Cox regression analyses were applied to predict the prognostic value of FKBP10 in patients with GC. Additionally, the protein expression levels of FKBP10 were validated by immunohistochemistry (IHC) in 40 GC and adjacent tissues. FKBP10 co‑expression network and bioinformatics analyses were then used to explore the potential functional mechanisms of FKBP10. The results revealed that the mRNA expression levels of FKBP10 were significantly increased in GC within the TCGA and GEO databases. Survival analysis revealed that high FKBP10 expression results in poorer overall survival and disease‑free survival (P<0.05). Multivariate cox regression analysis indicate FKBP10 as a dependent prognostic factor. The results of IHC indicated that the protein expression levels of FKBP10 were higher in GC tissues than in adjacent non‑GC tissues (P<0.001). Co‑expression networks and functional enrichment analysis suggested that FKBP10 may be involved in the development of GC via cell adhesion molecules and extracellular matrix‑receptor interaction pathways. Therefore, the findings of the present study indicated that FKBP10 is upregulated in GC tissues, and suggests its potential prognostic value. Therefore FKBP10 may be a potential therapeutic target for the treatment of GC.

Ovarian serous carcinoma (OC) is a common cause of mortality among gynecological malignancies. Although tumor‑infiltrating CD8 T cells are associated with a favorable prognosis of OC, the underlying mechanisms are not clearly understood. The present study identified the key genes and potential molecular mechanisms associated with CD8 T‑cell infiltration in OC. The score of CD8 T cells in The Cancer Genome Atlas dataset (376 samples from patients with OC) was estimated using the quanTIseq and MCP‑counter algorithms. Thereafter, a protein‑protein interaction network of differentially expressed genes was constructed and the hub genes were identified using cytoHubba in Cytoscape. The results revealed that signal transducer and activator of transcription 4 (STAT4) was strongly correlated with CD8 T‑cell infiltration in OC. Furthermore, the prognostic value of STAT4 in OC was verified by Kaplan‑Meier curve, and univariate and multivariate analyses. The biological functions of STAT4 were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, which revealed that STAT4 is closely related to cytokines in OC. Moreover, Spearman correlation analysis suggested that STAT4 was most positively correlated with CC chemokine ligand 5 (CCL5). CCL5 was revealed to be critical for orchestrating T‑cell infiltration in tumors. Moreover, immunohistochemistry and reverse transcription‑quantitative PCR showed that STAT4, CCL5 and CD8A (a marker for CD8 T cells) were closely related in OC. Moreover, in vitro analysis revealed that STAT4 knockdown led to a decrease in CCL5 expression and CD8 T‑cell migration. Taken together, the present study suggested that STAT4 may regulate CD8 T‑cell infiltration in OC tissues by inducing CCL5 secretion. Furthermore, STAT4 may be considered a promising prognostic biomarker for OC.

MicroRNAs (miRNAs or miRs) contribute to the development of various malignant neoplasms, including glioblastoma multiforme (GBM). The present study aimed to explore the pathogenesis of GBM and to identify latent therapeutic agents for patients with GBM, based on an in silico analysis. Gene chips that provide miRNA expression profiling in GBM were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) were also determined via the RobustRankAggreg algorithm. The target genes of DEMs were predicted and then intersected with GBM‑associated genes that were collected from the Gene Expression Profiling Interactive Analysis. Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the overlapping genes were then performed. Simultaneously, a connectivity map (CMap) analysis was performed to screen for potential therapeutic agents for GBM. A total of 10 DEMs (hsa‑miR‑196a, hsa‑miR‑10b, hsa‑miR‑196b, hsa‑miR‑18b, hsa‑miR‑542‑3p, hsa‑miR‑129‑3p, hsa‑miR‑1224‑5p, hsa‑miR‑876‑3p and hsa‑miR‑770‑5p) were obtained from three GEO gene chips (GSE25631, GSE42657 and GSE61710). Then, 1,720 target genes of the 10 miRNAs and 4,185 differently expressed genes in GBM were collected. By intersecting the aforementioned gene clusters, the present study identified 390 overlapping genes. GO and KEGG analyses of the 390 genes demonstrated that these genes were involved in certain cancer‑associated biological functions and pathways. Eight genes [(GTPase NRas (NRAS), calcium/calmodulin‑dependent protein kinase type II subunit Gamma (CAMK2G), platelet‑derived growth factor receptor alpha (PDGFRA), calmodulin 3 (CALM3), cyclin‑dependent kinase 6 (CDK6), calcium/calmodulin‑dependent protein kinase type II subunit beta (CAMK2B), retinoblastoma‑associated protein (RB1) and protein kinase C beta type (PRKCB)] that were centralized in the glioma pathway were selected for CMap analysis. Three chemicals (W‑13, gefitinib and exemestane) were identified as putative therapeutic agents for GBM. In summary, the present study identified three miRNA‑based chemicals for use as a therapy for GBM. However, more experimental data are needed to verify the therapeutic properties of these latent drugs in GBM.

Several studies have indicated that microRNAs (miRs) mediate multiple pathways associated with tumorigenesis and progression. Our preliminary study experimentally verified that miR‑146a‑5p has a role in the biological behavior of non‑small cell lung cancer (NSCLC) cells. To perform further investigation of miR‑146a‑5p, the present study evaluated miR‑146a‑5p by targeting its downstream gene tumor collagenase stimulatory factor (TCSF) to influence cell viability, proliferation and apoptosis in NSCLC. Online sequence prediction, a thorough search of the open source database The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC) of TCSF in clinical lung cancer tissues, and a dual‑luciferase assay, as well as assays to test viability, proliferation and apoptosis in vitro, were conducted to explain the targeted regulation association between miR‑146a‑5p and TCSF in NSCLC. The miRanda and TargetScanHuman database revealed that TCSF and miR‑146a‑5p had target binding sites. A luciferase reporter assay demonstrated that miR‑146a‑5p and TCSF did have complementary sequences (P<0.05). From the TCGA database, TCSF was highly expressed in lung adenocarcinoma and lung squamous cell carcinoma tissues when compared with normal lung tissues (P<0.05). Furthermore, the protein level of TCSF in cancerous lung tissues was determined by IHC, and it was concluded that TCSF protein was also upregulated in NSCLC tissues (P<0.001). A significant difference was identified following in vitro experiments for the NSCLC cell line A549, which revealed that miR‑146a‑5p and TCSF regulated cell viability, proliferation and apoptosis. In conclusion, the present study verified the target action association between TCSF and miR‑146a‑5p with high throughput data analysis and experimental results in NSCLC.