AG490 is a selective inhibitor of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. The present study examined its effects on the abnormal behavior of human keloid fibroblasts (HKFs) and evaluated its potential use in the treatment of keloids. Human normal fibroblasts (HNFs) and HKFs were treated with increasing concentrations of AG490. The proliferation of HNFs and HKFs was inhibited by AG490 in both a time‑ and concentration‑dependent manner by increasing apoptosis and inducing G1 cell cycle arrest. The downregulation of cyclin D1 and connective tissue growth factor (CTGF) expression was associated with a decrease in STAT3 expression in response to AG490. The effects of AG490 on TGF‑β‑stimulated fibroblasts, including HNFs, HKFs and hypertrophic scar fibroblasts (HSFs) were also evaluated. The TGF‑β1‑stimulated excessive proliferation and CTGF production were markedly inhibited by the application of AG490 in the HNFs, HSFs and HKFs. In addition, the STAT3‑specific decoy oligodeoxynucleotides (SODNs) were transfected into HKFs. The invasive ability of the SODN‑transfected HKFs was determined and the expression of extracellular matrix components was quantified. Similarly, SODNs blocked the constitutive activation of STAT3. SODNs inhibited the invasion and progression of HKFs, possibly via the upregulation of the expression of tissue inhibitor of metalloproteinase‑2 (TIMP‑2), and the downregulation of the expression of matrix metalloproteinase‑2 (MMP‑2) and vascular endothelial growth factor (VEGF). On the whole, the findings of the present study demonstrate that STAT3‑specific elimination, such as the application of AG490 and decoy ODNs, may serve as promising therapeutic strategies for the treatment of keloids.

The present study investigated the underlying molecular mechanism by which Buthus martensii Karsch chlorotoxin (BmK CT) inhibits the invasion and metastasis of glioma cells and the possibility of 131I‑labeled BmK CT (131I‑BmK CT) as a novel targeted agent for the treatment of glioma. The impact of BmK CT with and without 131I radiolabeling on the invasion and metastasis of glioma cells in vitro was studied. Cell viability was assessed using Cell Counting Kit‑8 and plate colony formation assays in order to confirm the cytotoxicity of BmK CT and 131I‑BmK CT at different concentrations. Transwell invasion and wound‑healing assays were conducted in order to investigate the inhibitory effects BmK CT and 131I‑BmK CT on cell migration and invasion. Furthermore, western blotting, ELISA immunofluorescence and a gelatin zymography assay were performed to evaluate changes in the protein expression levels of glioma cells following treatment with BmK CT or 131I‑BmK CT. The results indicated that BmK CT inhibits the invasion and metastasis of glioma cells via regulation of tissue inhibitor of metalloproteinase‑2 expression and that 131I‑BmK CT has the potential to be a novel targeted therapeutic drug for glioma.

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension‑independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl‑L‑arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes‑related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L‑NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end‑diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

The most common and aggressive type of brain cancer in adults is glioblastoma multiforme (GBM), and hypoxia is a common feature of glioblastoma. As the histological features of glioma include capillary endothelial cell proliferation, they are highly prone to invading the surrounding normal brain tissue, which is often one of the reasons for the failure of treatment. However, the mechanisms involved in this process are not fully understood. MicroRNAs (miRs) are a class of non‑coding RNA that are able to inhibit the malignant progression of tumor cells through the regulation of downstream genes. In the present study, the low expression of miR‑576‑3p was detected in glioma samples and hypoxia‑treated glioma cells using a reverse transcription‑quantitative polymerase chain reaction. The present study focused on the effects of miR‑576‑3p on hypoxia‑induced glioma. The results of the functional experiments revealed that the overexpression of miR‑576‑3p significantly inhibited the migration and pro‑angiogenic abilities of the glioma cells under hypoxic conditions (P<0.05) compared with in the lentivirus‑miR‑negative control group. Furthermore, luciferase reporter gene assays were used to validate the hypothesis that miR‑576‑3p interacts with the 3'‑untranslated region of hypoxia‑inducible factor‑1α (HIF‑1α) and induces a reduction in the protein levels of matrix metalloproteinase‑2 and vascular endothelial growth factor. Rescue experiments demonstrated that the restoration of HIF‑1α expression attenuated the effect of miR‑576‑3p on the migration and proangiogenic abilities of glioma cells. In conclusion, the present study confirms that miR‑576‑3p is a novel GBM inhibitor and its inhibition of the migration and proangiogenic capacity of hypoxia‑induced glioma cells is mediated by HIF‑1α.

The incidence and recurrence rates of ovarian cancer are still high, and once the disease metastasizes, it is nearly always fatal. Cullin 4A (CUL4A) serves a significant role in tumourigenesis and tumour progression; however, the effect and mechanisms underlying CUL4A overexpression are still unknown. The role of microRNAs (miRs) in the regulation of metastatic capability in ovarian cancer cell lines was investigated. The interaction between miR‑377 and CUL4A was investigated using bioinformatics analyses and dual‑luciferase reporter assays. Furthermore, miR‑377 mRNA and protein levels were detected using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively and cell migration and invasion were detected using a Transwell assay. Results revealed that CUL4A expression was negatively associated with miR‑377 levels in ovarian cancer tissues and cell lines. Through in silico analysis, the targeting effect of miR‑377 on CUL4A was verified. Ectopic expression of miR‑377 in SKOV3 cells downregulated the level of CUL4A, and significantly reduced the migratory ability of the cells. miR‑377 overexpression led to reduced activity of the Wnt/β‑catenin signaling pathway, and regulated the expression of matrix metalloproteinase‑2, and 9, and epithelial‑mesenchymal transition (EMT)‑associated protein. These results suggested that miR‑377 is a significant negative regulator of CUL4A that controls cancer cell progression in ovarian cancer cell lines.

Glioblastomas are highly malignant gliomas that are extremely invasive with high rates of recurrence and mortality. It has been reported that activating transcription factor 3 (ATF3) is expressed in elevated levels in multiple malignant tumors. The purpose of this study was to investigate the function of ATF3 in the development of glioma and its clinical significance. Immunohistochemical staining, western blot analysis and RT-qPCR revealed that the mRNA and protein levels of ATF3 and matrix metalloproteinase 2 (MMP2) were higher in the glioma than in the normal human brain tissues, and that their levels were proportional to the pathological grades. By contrast, the mRNA and protein levels of mammary serine protease inhibitor (maspin; SERPINB5) were significantly lower in the glioma than in the normal brain tissue, and maspin expression was inversely proportional to the glioma pathological grade. The transfection of U373MG glioblastoma cells with ATF3-siRNA induced a number of changes in cell behavior; the cell proliferative activity was decreased and flow cytometry revealed an increased proportion of cells arrested in the G0/G1 phase of the cell cycle. In addition, TUNEL staining indicated an increased proportion of cells undergoing apoptosis and Transwell assays revealed impaired cell mobility. The sizes of the tumors grown as xenografts in nude mice were also significantly reduced by treatment of host mice with ATF3-siRNA. Taken together, these results suggest that ATF3 promotes the progression of human gliomas.