Methamphetamine (MA) is a highly abused amphetamine‑like psychostimulant. At present, the mechanisms underlying MA‑induced cardiotoxicity are poorly understood. The cardiotoxic effects have yet not been clearly elucidated with respect to the apoptotic pathway. Insulin‑like growth factor binding protein‑5 (IGFBP5) is important for cell growth control and the induction of apoptosis. The aim of the present study was to analyze whether IGFBP5 is involved in MA‑induced apoptosis as a novel target. MA‑induced apoptosis was observed in neonatal rat ventricular myocytes (NRVMs) in a concentration‑dependent manner using a terminal deoxyribonucleotide transferase‑mediated dUTP nick end‑labeling assay. Using reverse transcription polymerase chain reaction and western blotting, MA was demonstrated to induce concentration‑dependent increases in the expression of IGFBP5. Silencing IGFBP5 with small interfering RNA significantly reduced apoptosis and suppressed the expression of caspase‑3 in NRVMs following treatment with MA. To the best of our knowledge, the present study provided the first evidence suggesting that IGFBP5 is a potential therapeutic target in MA‑induced apoptosis in vitro, providing a foundation for future in vivo studies.

The present study was conducted in order to improve gene expression efficiency of insulin‑like growth factor‑1 (IGF‑1)‑transfected mesenchymal stem cells (MSCs) using a non‑viral carrier and a simplified method of dual gene selection. The therapeutic efficacy of this MSC‑based IGF‑1/enhanced green fluorescent protein (EGFP) dual gene sorting system was evaluated in a rat myocardial infarction (MI) model. IGF‑1 and EGFP genes were expressed in MSCs in vitro. The purity of dual gene‑expressing MSCs was 95.1% by fluorescence‑activated cell sorting. Transfected MSCs injected into rats were identified based on green fluorescence, with an increased signal intensity observed in rats injected with sorted cells, compared with unsorted cells. IGF‑1 expression levels were additionally increased in the sorted group, and decreases in infarct size, fibrotic area and fraction of apoptotic cells were observed. These results demonstrated that IGF‑1 overexpression protects against fibrosis and apoptosis in the myocardium and reduces infarct size following MI. Additionally, the present vector sorting system may potentially be applied to other types of stem cell‑based gene therapy.

Vasohibin‑2 (VASH2) is an angiogenic factor, and has been previously reported to be a cancer‑related gene, with cytoplasmic and karyotypic forms. In the current study VASH2 expression in human breast cancer tissue and adjacent non‑cancerous tissue was investigated with immunohistochemistry. MCF‑7 and BT474 human breast cancer cells were transfected with lentiviral constructs to generate in vitro VASH2 overexpression and knockdown models. In addition, BALB/cA nude mice were inoculated subcutaneously with transfected cells to generate in vivo models of VASH2 overexpression and knockdown. The effect of VASH2 on cell proliferation was investigated using a bromodeoxyuridine assay in vitro and immunohistochemistry of Ki67 in xenograft tumors. Growth factors were investigated using a human growth factor array, and certain factors were further confirmed by an immunoblot. The results indicated that the expression level of cytoplasmic VASH2 was higher in breast cancer tissues with a Ki67 (a proliferation marker) level of ≥14%, compared with tissues with a Ki67 level of <14%. VASH2 induced proliferation in vitro and in vivo. Four growth factors activated by VASH2 were identified as follows: Fibroblast growth factor 2 (FGF2), growth/differentiation factor‑15 (GDF15), insulin‑like growth factor‑binding protein (IGFBP)3 and IGFBP6. FGF2 and GDF15 may contribute to VASH2‑induced proliferation. The current study identified a novel role for VASH2 in human breast cancer, and this knowledge suggests that VASH2 may be a novel target in breast cancer treatment.

GC binding factor 2 (GCF2) is a transcriptional repressor that inhibits the transcription of GC‑rich promoters, thereby regulating biological processes, including proliferation. However, the role of GCF2 in vascular smooth muscle cells (VSMCs) remains unclear. The level of α‑smooth muscle (α‑SM) actin was determined by immunofluorescence. Cell viability, migration and invasion were analyzed using Cell Counting Kit‑8, wound healing and Transwell assays, respectively. Apoptosis and cell cycle progression were determined using flow cytometry. The expressions of Bcl‑2, Bax, cleaved caspase‑3, cyclin E, CDK2 and the CDK inhibitor p21 were determined by reverse transcription‑quantitative (RT‑q)PCR and western blot analysis. RT‑qPCR was performed to analyze the levels of GCF2 and western blot analysis was conducted to determine the phosphorylation levels of PI3K and AKT. α‑SM actin was found to be expressed in VSMCs. Cell viability, migration and invasion were inhibited by small interfering (si)RNA targeting GCF2. Changes in the expression levels of Bcl‑2, Bax and cleaved caspase‑3 showed that the pro‑apoptotic capacity of the cells was increased by siGCF2. Cell cycle arrest in the G0/G1 phase was induced by siGCF2, which was accompanied by changes in the levels of cyclin E, CDK2 and p21. Furthermore, phosphorylation of PI3K and AKT was suppressed by siGCF2. However, the inhibitory effects of siGCF2 on cell viability, migration and invasion were increased by insulin‑like growth factor 1, which is a specific agonist of AKT. The anti‑proliferative activity of siGCF2 may be associated with the PI3K/AKT pathway in VSMCs.

Diffuse large B‑cell lymphoma (DLBCL) remains difficult to treat clinically due to its highly aggressive characteristics. Insulin‑like growth factor 2 mRNA‑binding protein 2 (IGF2BP2) and 5'‑nucleotidase domain‑containing 2 (NT5DC2) have been suggested as potential regulators in numerous types of cancer. The present study aimed to determine whether downregulation of IGF2BP2 and NT5DC2 suppresses cell proliferation, and induces cell cycle arrest and apoptosis in DLBCL cells by regulating the p53 signaling pathway. The expression levels of IGF2BP2 and NT5DC2 in DLBCL cells were determined by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Transfection of cells with IGF2BP2 overexpressing plasmids and NT5DC2 interference plasmids was performed, and the efficacy of transfection was confirmed by RT‑qPCR and western blot analysis. The viability, proliferation, cell cycle progression and apoptosis of DLBCL cells were analyzed by Cell Counting Kit‑8 assay, 5‑bromo‑2‑deoxyuridine staining and flow cytometry. RNA pull‑down and immunoprecipitation assays were used to verify the binding of IGF2BP2 and NT5DC2. The expression levels of apoptosis, cell cycle and p53 pathway‑associated proteins were determined by western blotting. The results revealed that NT5DC2 expression was increased in DLBCL cell lines and was the highest in OCI‑Ly7 cells. IGF2BP2 expression was also increased in OCI‑Ly7 cells and IGF2BP2 bound to NT5DC2. Knockdown of NT5DC2 suppressed cell viability and proliferation, induced cell cycle arrest and promoted apoptosis in DLBCL cells, which was reversed by upregulation of IGF2BP2. In addition, knockdown of NT5DC2 increased the expression of p53 and p21, but suppressed the expression of proliferating cell nuclear antigen, CDK4 and cyclin D1; these effects were reversed by upregulation of IGF2BP2. In conclusion, knockdown of NT5DC2 suppressed cell viability and proliferation, induced cell cycle arrest and promoted apoptosis in DLBCL cells by regulating the p53 signaling pathway and these effects were reversed by upregulation of IGF2BP2.

Premature rupture of membranes (PROM) is a common pregnancy complication that frequently results in maternal and perinatal morbidity. The present methods for diagnosing PROM do not satisfy clinical requirements. The present study aimed to examine the proteome profile of amniotic fluid (AF) and maternal plasma, screen unique proteins in AF, and evaluate their diagnostic value for diagnosing PROM. The proteome profiles of AF and maternal plasma were examined via liquid chromatography coupled with tandem mass spectrometry‑based proteomic techniques. The protein expression levels of diagnostic candidates in AF, maternal plasma and vaginal fluid were determined by ELISA analysis and Magnetic Luminex® screening assays. The diagnostic value of potential biomarkers was evaluated using receiver operating characteristic curves. A lateral flow assay was developed based on colloidal gold immunochromatography technology. The present study identified 540 unique proteins in AF, 12 of which were chosen for further detection. The present results demonstrated that expression levels of pulmonary surfactant‑associated protein B, BPI fold‑containing family A member 1, zymogen granule protein 16 homolog B, EGF‑containing fibulin‑like extracellular matrix protein 1, keratin, type II cytoskeletal 4, keratin, type I cytoskeletal 19, placental protein 14 (PP14), insulin‑like growth factor‑binding protein 2, mesothelin and serpin family B member 3 were significantly higher in AF compared with in maternal plasma (P<0.01). Furthermore, PP14 was observed to have excellent diagnostic accuracy for preterm PROM (PPROM), with a respective sensitivity and specificity of 100 and 87.5% when the cutoff value was 0.008 µg/ml. The PP14‑based lateral flow assay demonstrated a visual detection threshold of 0.008 µg/ml. The results from the present study suggested that PP14 may be a novel potential biomarker for PPROM, and may be developed into a lateral flow assay for bedside application to rapidly diagnose PPROM.

Oxidative stress serves important roles in cardiac injury during the process of ischemia/reperfusion (I/R). Y‑box protein 1 (YB1), a member of the highly conserved Y‑box protein family, is closely associated with inflammation and stress responses by regulating gene transcription, RNA splicing and mRNA translation. However, the roles of YB1 in oxidative stress‑induced myocardial‑I/R (M‑I/R) injury are unknown. The aim of the present study was to examine the effects of YB1 on H2O2‑induced cardiomyocyte injury and its underlying mechanism. The results demonstrated that YB1 expression was upregulated during H2O2‑induced myocardial injury. YB1 knockdown through transfection of small interfering RNA significantly aggravated cardiac cell apoptosis. Furthermore, YB1 knockdown significantly reversed the H2O2‑mediated increase in phosphorylated signal transducer and activator of transcription (STAT)3, but did not affect the phosphorylation of P38, extracellular signal‑regulated kinases 1/2, c‑Jun N‑terminal kinases, P65, Janus kinase 1 and 2 or STAT1. Moreover, protein co‑immunoprecipitation and RNA‑binding protein immunoprecipitation assays revealed that YB1 interacted with protein inhibitor of activated STAT 3 (PIAS3) mRNA but not its translated protein. YB1 overexpression may have promoted PIAS3 mRNA decay, decreasing PIAS3 protein levels, and therefore increased the levels of phosphorylated STAT3. Finally, YB1 knockdown, mediated by a lentivirus carrying YB1 targeted short hairpin RNA, significantly decreased left ventricle percentage fractional shortening and ejection fraction values, while increasing the infarct sizes in a rat model of M‑I/R injury. These results demonstrated for the first time (to the best of our knowledge) that YB1 may protect cardiac myocytes against H2O2 or M‑I/R‑induced injury by binding to PIAS3 mRNA and resulting in the phosphorylation of STAT3.

Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of breast tumor because of its low pathogenicity and immunogenicity. Our previous study demonstrated that insulin‑like growth factor‑binding protein 2 (IGFBP‑2) was highly expressed in patients with breast metastasis. In the present study, the effects of recombinant AAV2 on the growth and metastasis of breast cancer cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and rAAV2‑ZsGreen‑shRNA‑hIGFBP‑2 were used to transfect MDA‑MB‑468, and MCF‑10A cells respectively, and observed that these virus could not penetrate the normal human breast epithelia MCF‑10A cell line. To investigate the effect of the recombinant virus on chemotherapeutics, paclitaxel was added to MDA‑MB‑468 cells and it was demonstrated that rAAV2‑ZsGreen‑shRNA‑hIGFBP-2-infected MDA-MB-468 cells were highly chemosensitive to paclitaxel compared with rAAV2‑ZsGreen‑shRNA‑scramble‑injected cells. In addition, it was demonstrated that the invasive ability of rAAV2‑ZsGreen‑shRNA‑hIGFBP‑2‑infected MDA-MB-468 cells was highly impaired compared with the rAAV2‑ZsGreen‑shRNA‑scramble group. In the nude mice xenografts, the rAAV2‑ZsGreen‑shRNA‑hIGFBP‑2 injection inhibited tumor growth and Ki‑67 expression was significantly downregulated compared with the scramble group. Following IGFBP‑2 knockdown using rAAV2-ZsGreen-shRNA-hIGFBP‑2, matrix metalloproteinase‑2 expression was significantly reduced in tumor tissues compared with that in rAAV2‑ZsGreen‑shRNA‑scramble treated tumor tissues. These findings have provided a direction for the application of novel AAV2‑based therapeutics for treating aggressive triple‑negative breast cancer types.

Sensorineural hearing loss is prevalent in patients receiving cisplatin therapy. Tetramethylpyrazine (Tet) and tanshinone IIA (Tan IIA) have protective roles against hearing impairment or ototoxicity. The present study aimed to investigate the molecular mechanisms underlying cisplatin‑induced ototoxicity and the protective effect of Tet and Tan IIA against it. House Ear Institute‑Organ of Corti 1 auditory cells were treated with titrating doses of Tan IIA, Tet, and cisplatin. In a cell viability assay, cisplatin, Tan IIA and Tet had IC50 values of 42.89 µM, 151.80 and 1.04x103 mg/l, respectively. Tan IIA augmented cisplatin‑induced cytotoxicity. However, Tet concentrations <75 mg/l attenuated cisplatin‑induced cytotoxicity and apoptosis. Moreover, RNA sequencing analysis was carried out on auditory cells treated for 30 h with 30 µM cisplatin alone for 48 h or combined with 37.5 mg/l Tet for 30 h. Differentially expressed genes (DEGs) induced in these conditions were identified and examined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Cisplatin increased the expression of genes related to the p53 and FoxO pathways, such as Fas, p21/CDKN1A, and Bcl‑2 binding component 3, but decreased the expression of insulin‑like growth factor 1 (IGF1), as well as genes in the histone (Hist)1 and Hist2 clusters. Treatment with Tet downregulated FOXO3 and Bcl‑2 binding component 3, and increased the expression of IGF1. Moreover, Tet upregulated genes associated with Wnt signaling, but not p53‑related genes. Thus, the otoprotective properties of Tet might be mediated by activation of Wnt and IGF1 signaling, and inhibition of FoxO signaling.

Recurrent spontaneous abortion (RSA) occurs in 1‑5% of parturients. The sustained therapy and research for RSA is expensive, which is a serious issue faced by both patients and doctors. The aim of the present study was to detect protein expression profiles in the serum of RSA patients and healthy controls, and to identify potential biomarkers for this disease. A 1,000‑protein microarray consisting of a combination of Human L‑507 and L‑493 was used. The microarray data revealed that eight serum protein expression levels were significantly upregulated and 143 proteins were downregulated in RSA patients compared with the healthy controls. ELISA individually validated 5 of these 151 proteins in a larger cohort of patients and control samples, demonstrating a significant decrease in insulin‑like growth factor‑binding protein‑related protein 1 (IFGBP‑rp1)/IGFBP‑7, Dickkopf‑related protein 3 (Dkk3), receptor for advanced glycation end products (RAGE) and angiopoietin‑2 levels in patients with RSA. Sensitivity and specificity analyses were calculated by a receiver operating characteristics curve, and were revealed to be 0.881, 0.823, 0.79 and 0.814, with diagnostic cut‑off points of 95.44 ng/ml for IFGBP‑rp1, 32.84 ng/ml for Dkk3, 147.27 ng/ml for RAGE and 441.40 ng/ml for angiopoietin‑2. The present study indicated that these four proteins were downregulated in RSA samples and may be useful as biomarkers for the prediction and diagnosis of RSA. Subsequent studies in larger‑scale cohorts are required to further validate the diagnostic value of these markers.

The antioxidant capability of herbal remedies has attracted widespread attention, but their molecular mechanisms in a muscle atrophy model have not been explored. The aim of the present study was to compare the bioactivity of sucrose challenged mice following treatment with ATG‑125. Here, through a combination of transcriptomic and biomedical analysis, herbal formula ATG‑125, a phytochemical‑rich formula, was identified as a protective factor against muscle atrophy in sucrose challenged mice. Gene ontology (GO) identified differentially expressed genes that were primarily enriched in the 'negative regulation of proteolysis', 'cellular amino acid metabolic process', 'lipoprotein particle' and 'cell cycle', all of which were associated with the ATG‑125‑mediated prevention of muscle atrophy, particularly with regard to mitochondrial biogenesis. In skeletal muscle, a set of mitochondrial‑related genes, including angiopoietin‑like 4, nicotinamide riboside kinase 2 (Nmrk2), pyruvate dehydrogenase lipoamide kinase isozyme 4, Asc‑type amino acid transporter 1 and mitochondrial uncoupling protein 3 (Ucp3) were markedly upregulated following ATG‑125 intervention. An increase in Nmrk2 and Ucp3 expression were noted after ATG‑125 treatment, in parallel with upregulation of the 'nicotinate and nicotinamide metabolism' pathway, as determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, KEGG pathway analysis revealed the downregulation of 'complement and coagulation cascades', 'cholesterol metabolism', 'biosynthesis of amino acids' and 'PPAR signaling pathway', which were associated with the downregulation of serine (or cysteine) peptidase inhibitor clade A member (Serpina)3, Serpina1b, Serpina1d, Serpina1e, apolipoprotein (Apo)a1 and Apoa2, all of which were cardiovascular and diabetes‑associated risk factors and were regulated by ATG‑125. In addition, ATG‑125 treatment resulted in downregulated mRNA expression levels of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2, troponin‑I1, troponin‑C1 and troponin‑T1 in young adult gastrocnemius muscle compared with the sucrose group. Nuclear factor‑κB‑hypoxia inducible factor‑1α‑TGFβ receptor type‑II‑vascular endothelial growth factor staining indicated that ATG‑125 decreased sucrose‑induced chronic inflammation. ATG‑125 was sufficient to prevent muscle atrophy, and this protective effect may be mediated through upregulation of AKT phosphorylation, upregulating the insulin growth factor‑1R‑insulin receptor substrate‑PI3K‑AKT pathway, which in turn resulted in a forkhead box O‑dependent decrease in protein degradation pathways, including regulation of atrogin1 and E3 ubiquitin‑protein ligase TRIM63. Peroxisome‑proliferator activated receptor γ coactivator 1α (PGC1α) was decreased in young adult mice challenged with sucrose. ATG‑125 treatment significantly increased PGC1α and significantly increased UCP‑1,2,3 expression levels, which suggested ATG‑125 poised the mitochondria for uncoupling of respiration. This effect is consistent with the increased SIRT1 levels and may explain an increase in mitochondria biogenesis. Taken together, the present study showed that ATG‑125, as an integrator of protein synthesis and degradative pathways, prevented muscle wasting.

Medulloblastoma is the most common malignant brain tumor of the central nervous system among children. Medulloblastoma is an embryonal tumor, of which little is known about the pathogenesis. Several efforts have been made to understand the molecular aspects of its tumorigenic pathways; however, these are poorly understood. microRNA (miRNA), a type of non‑coding short RNA, has been proven to be associated with a number of physiological processes and pathological processes of serious diseases, including brain tumors. Differentially expressed miRNAs serve an important role in numerous types of malignancy. The present study aims to define a differentially expressed set of miRNAs in medulloblastoma tumor tissue, compared with normal samples, to improve the understanding of the tumorigenesis. It was identified that 22 miRNAs were upregulated and 26 miRNAs were downregulated in the tumor tissue compared with the normal group. However, when the medulloblastoma tissue was compared with normal cerebellum tissue, 9 miRNAs were identified to be up or downregulated in the tumor samples. The differentially expressed miRNAs in the tumor tissue were identified in order to clarify the networks and pathways of tumorigenesis using Ingenuity Pathway Analysis. Subsequently, key regulatory genes associated with the development of medulloblastoma were identified, including tumor protein p53, insulin like growth factor 1 receptor, argonaute 2, mitogen‑activated protein kinases 1 and 3, sirtuin 1 and Y box binding protein 1.

Dilated cardiomyopathy (DCM) is a primary cardiomyopathy with high mortality. The aim of the present study was to identify the related genes in DCM. The four expression profiles (GSE17800, GSE21610, GSE42955 and GSE79962) downloaded from the Gene Expression Omnibus (GEO) database were analyzed using RankProd and metaMA R packages to identify differentially expressed genes (DEGs). DEGs were uploaded to the Database for Annotation, Visualization and Integrated Discovery (DAVID), for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein‑protein interaction (PPI) network of the DEGs was constructed using the STRING database. In addition, hub genes were identified using the Cytoscape plugin cytoHubba. A mouse DCM model, which established via intraperitoneal injection with doxorubicin (DOX), was used to validate the hub genes. A total of 898 DEGs were identified across the four microarrays. Furthermore, GO analysis demonstrated that these DEGs were mainly enriched in cell adhesion, negative regulation of cell proliferation, negative regulation of apoptotic process and potassium ion transport. In addition, KEGG analysis revealed that DEGs were mainly enriched in the ECM‑receptor interaction, the p53 signaling pathway, cardiac muscle contraction and the hypoxia‑inducible factor signaling pathway. Proenkephalin (PENK), chordin like 1 (CHRDL1), calumenin (CALU), apolipoprotein L1, insulin‑like growth factor binding protein 3 (IGFBP3) and ceruloplasmin (CP) were identified as hub genes in the PPI network. Furthermore, the expression levels of PENK, CHRDL1, IGFBP3, CP and CALU in hearts with DCM were validated using a mouse model. In conclusion, the present study identified six hub genes related to DCM. Therefore, the present results may provide a potential mechanism for DCM involving these hub genes, which may serve as biomarkers for screening and diagnosis in the clinic.

Hepatocellular carcinoma (HCC) has become a major cause of cancer‑related mortality worldwide. Circular RNAs (circRNAs) are non‑coding RNAs that serve important roles in multiple cancers. However, the role of circRNAs in HCC remains largely unknown. In the present study, a circRNA microarray dataset of HCC samples, GSE97332, was downloaded from the gene expression omnibus database. Following data preprocessing, differentially expressed circRNAs between HCC tissues and normal tissues were determined using GEO2R. The circRNA‑miRNA interactions were predicted by the miRanda database. The miRTarbase database was used to search for target genes of the miRNAs. A circRNA‑miRNA‑mRNA network was constructed using Cytoscape based on the obtained circRNA, miRNA and mRNA. In this network, the upregulated circRNA hsa_circRNA_100084 was found to be involved in a competing endogenous relationship of hsa_circRNA_100084‑hsa‑miR‑23a‑5p‑ insulin‑like growth factor 2 (IGF2). The differential expression of hsa_circRNA_100084, hsa‑miR‑23a‑5p and IGF2 in HCC tissues and liver cancer cells was validated by reverse transcription‑quantitative PCR. Additionally, the interactions between hsa‑miR‑23a‑5p with hsa_circRNA_100084 and IGF2 were validated by dual‑luciferase reporter assays. Knocking down hsa_circRNA_100084 inhibited the proliferation, migration and invasion of liver cancer cells, while the simultaneous overexpression of IGF2 reversed the effects of hsa_circRNA_100084 knockdown. The results show that hsa_circRNA_100084 could promote the expression of IGF2 by acting as a sponge of hsa‑miR‑23a‑5p in liver cancer cells.

The present study aimed to analyze the effects and underlying mechanisms of microRNA (miR)‑29‑3p on the proliferation and secretory abilities of prolactinoma cells by targeting insulin‑like growth factor (IGF)‑1/β‑catenin. The relationship between miR‑29a‑3p and the survival of prolactinoma cells was analyzed with the Kaplan‑Meier method in reference to The Cancer Genome Atlas. The expression levels of miR‑29a‑3p and IGF‑1 in MMQ and GH3 cells were detected. A dual‑luciferase reporter gene assay was performed to verify the combination of miR‑29a‑3p and IGF‑1. Cells were transfected with a miR‑29a‑3p mimic and/or IGF‑1 pcDNA3.1 to analyze the effects on the proliferation, apoptosis and secretion of prolactin (PRL) and growth hormone (GH) of prolactinoma cells. The effects on β‑catenin in the cytoplasm and nucleus were investigated by western blot analysis. The results showed that miR‑29a‑3p expression was low in MMQ and GH3 cells. Overexpression miR‑29a‑3p inhibited IGF‑1 mRNA and protein expression. miR‑29a‑3p inhibited cell proliferation and PRL and GH expression, and promoted apoptosis by inhibiting IGF‑1. Increasing the expression of miR‑29a‑3p increased β‑catenin levels in the cytoplasm, whereas IGF‑1 promoted β‑catenin activation and entry into the nucleus, and reversed the inhibitory effects of miR‑29a‑3p on β‑catenin. To conclude, miR‑29a‑3p inhibited the proliferation and secretory abilities of prolactinoma cells by inhibiting nuclear translocation of β‑catenin via a molecular mechanism that is inseparable from IGF‑1.

The increasing rates of morbidity and mortality caused by ischemic heart disease pose a serious threat to human health. Long non‑coding (lnc)RNA small nucleolar RNA host gene 1 (SNHG1) has a protective effect on the myocardium. In the present study, the role of lncRNA SNHG1 in myocardial ischemia reperfusion injury (MIRI) and the underlying mechanisms were investigated. After hypoxia/reoxygenation (H/R) induction, the expression levels of lncRNA SNHG1 were detected using reverse transcription‑quantitative PCR. After lncRNA SNHG1 overexpression via cell transfection, cell viability was detected using an MTT assay, apoptotic rates were detected using TUNEL staining, apoptosis‑related protein expression levels were detected using western blotting and respective kits were used to measure the oxidative stress levels. The Encyclopedia of RNA Interactomes database predicted the presence of binding sites between lncRNA SNHG1 and microRNA (miR)‑450b‑5p, and between miR‑450b‑5p and insulin‑like growth factor 1 (IGF1). These interactions were then verified using luciferase reporter assays. Subsequently, the regulatory mechanism underlying the lncRNA SNHG1/miR‑450b‑5p/IGF1 axis in MIRI was investigated by overexpressing miR‑450b‑5p and knocking down IGF1 expression in H/R‑induced cells. Finally, the expression of PI3K/Akt signaling pathway‑related proteins was detected using western blotting. lncRNA SNHG1 expression was significantly downregulated in H/R‑induced AC16 cells. lncRNA SNHG1 overexpression significantly inhibited apoptosis and decreased oxidative stress levels in H/R‑induced AC16 cells, which was mediated via regulation of the miR‑450b‑5p/IGF1 axis and activation of the PI3K/Akt signaling pathway. Therefore, the present study suggested that activation of the PI3K/Akt signaling pathway via the lncRNA SNHG1/miR‑450b‑5p/IGF1 axis inhibited the apoptosis and oxidative stress levels of H/R‑induced AC16 cells.

The use of propranolol for the treatment of infantile hemangioma (IH) has been widely investigated in recent years. However, the underlying therapeutic mechanism of propranolol for the treatment of IH remains poorly understood. The aim of the present study was to investigate the expression of proteins regulated by cellular tumor antigen p53 (p53) in associated apoptosis pathways in IH endothelial cells (HemECs) treated with propranolol. Furthermore, the present study aimed to investigate the exact apoptotic pathway underlying the therapeutic effect of propranolol against IH. In the present study, HemECs were subcultured and investigated using an inverted phase contrast microscope, immunocytochemical staining and a scanning electron microscope (SEM). Experimental groups and blank control groups were prepared. All groups were subjected to drug treatment. A high p53 expression model of HemECs was successfully established via transfection, and a low p53 expression model of HemECs was established using pifithrin‑α. The apoptosis rate of each group was determined using Annexin V‑fluorescein isothiocyanate/propidium iodide double staining and flow cytometry. The expression levels of downstream proteins regulated by p53 [tumour necrosis factor receptor superfamily member 6 (FAS), p53‑induced death domain‑containing protein (PIDD), death receptor 5 (DR5), BH3‑interacting domain death agonist (BID), apoptosis regulator BAX (BAX), p53 unregulated modulator of apoptosis (PUMA), phosphatidylinositol‑glycan biosynthesis class S protein (PIGS), and insulin‑like growth factor‑binding protein 3 (IGF‑BP3)] were revealed in the experimental and control groups via western blotting. Microscopic observation revealed the growth of an adherent monolayer of cells, which were closely packed and exhibited contact inhibition. Immunocytochemical staining demonstrated increased expression of clotting factor VIII. SEM analysis revealed presence of Weibel‑Palade bodies. The results of the analyses verified that the cultured cells were HemECs. The staining of the samples resulted in a significantly increased rate of apoptosis in experimental groups compared with the blank control group. This result suggested that there is an association between p53 expression and the rate of apoptosis of propranolol‑treated HemECs. The results of the western blot analysis demonstrated an upregulation of BAX expression and a downregulation of IGF‑BP3 expression in the HemECs treated with propranolol. There were no significant differences in the expression levels of FAS, DR5, PIDD, BID, PUMA and PIGS between experimental and control groups. This result suggests that p53 has an important role in HemEC apoptosis. The results of the present study additionally suggest that the propranolol‑induced HemEC apoptosis pathway is a mitochondrial apoptosis pathway and is regulated by p53‑BAX signaling.

The mortality rate of ovarian cancer (OC) is the highest among the different types of female reproductive system cancers. SIX homeobox 4 (SIX4), a member of the homeobox family, subfamily SIX, fulfills an important role in metastasis and angiogenesis in a variety of types of cancer. The aim of the present study was to investigate both the effects and the underlying mechanism of SIX4 on angiogenesis in OC. The Gene Expression Profiling Interactive Analysis and Encyclopedia of RNA Interactomes databases were employed to predict the expression levels of SIX4 in OC tissues, and its association with the overall survival (OS) rate of patients with OC. The expression levels of SIX4 in OC cell lines were detected by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Following silencing of SIX4, the proliferation, invasion, migration and angiogenesis of OC cells were investigated via Cell Counting Kit‑8, colony formation, wound healing, Transwell and tube formation assays. Subsequently, the levels of insulin‑like growth factor 2 mRNA binding protein 3 (IGF2BP3) in OC cell lines were detected by RT‑qPCR and western blot analysis. The ability of IGF2BP3 to bind to SIX4 mRNA was detected via an RNA immunoprecipitation assay, and the stability of SIX4 mRNA was assessed by RT‑qPCR following Actinomycin D treatment. Finally, the effects of transfection of sh‑SIX4 and overexpression of IGF2BP3 simultaneously were examined to further delineate the mechanism involved. It was revealed that SIX4 was highly expressed in OC tissues and cells, and its expression was associated with low OS rates in patients with OC. SIX4 knockdown with short hairpin RNA inhibited the proliferation, migration and invasion of cells, as well as angiogenesis. In addition, IGF2BP3 overexpression led to an improvement in the stability of SIX4 mRNA. Overexpression of IGF2BP3 also reversed the inhibitory effect of SIX4 interference on the malignant phenotypes of OC cells. Taken together, the results of the present study demonstrated that IGF2BP3‑stabilized SIX4 promoted the proliferation, metastasis and angiogenesis of SKOV3 cells.