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Hepatocellular carcinoma (HCC) is the leading cause of cancer‑associated death in the world. Chemotherapy remains the primary treatment method for HCC. Despite advances in chemotherapy and modalities, recurrence and resistance limit therapeutic success. Salidroside (Sal), a bioactive component extracted from the rhizome of

Paired box 6 (PAX6), a highly conserved transcription factor, is important in glioma. However, the molecular mechanisms involved remain unclear. The present study demonstrated that the expression of PAX6 was significantly reduced with the malignancy of glioma and also identified PAX6 as a novel target of microRNA (miR)‑335, which was significantly upregulated in glioma. The inhibition of miR‑335 increased the protein expression of PAX6, whereas the upregulation of miR‑335 suppressed its expression in human glioma U251 and U87 cells. Furthermore, upregulation of miR-335 promoted U251 cell proliferation, colony formation and invasion, which was reversed by the overexpression of PAX6. Furthermore, the present study demonstrated that the effect of miR‑335 on U251 cell invasion was via the modulation of matrix metalloproteinase (MMP)‑2 and MMP‑9 expression by targeting PAX6. In conclusion, the present study demonstrated that PAX6, as a novel target of miR‑335, has an anti‑oncogenic function in glioma, and thus PAX6 may serve as a therapeutic target for glioma.

Glioblastoma (GBM) is the predominant and most fatal type of brain tumor in adults. The prognosis of GBM remains poor despite advances in surgery, chemotherapy and radiotherapy. It is common that patients with GBM exhibit innate or acquired resistance to temozolomide (TMZ), a standard chemotherapeutic agent for GBM, and a previous report demonstrated that miRNA-233 (miR-223) promotes the growth and invasion of GBM cells by targeting tumor suppressor paired box 6 (PAX6). The present study explored the effect of TMZ on miR-223/PAX6 signaling in addition to the effect of miR-223/PAX6 signaling on TMZ chemoresistance in human GBM cells. Luciferase reporter assays confirmed that miR-223 directly targets PAX6 through binding to its 3′-untranslated region. TMZ reduced the expression level of miR-223 in a concentration-dependent manner in U251 and U118 GBM cells, which led to increased expression of PAX6. miR-223 and/or PAX6 were overexpressed and knocked down in U251 and U118 cells, and the half maximal inhibitory concentration (IC50) of TMZ and cell proliferation under TMZ treatment were used as measures of TMZ chemoresistance. The results demonstrated that overexpression of miR-223 in GBM cells markedly decreased TMZ-induced inhibition of cell proliferation and increased TMZ IC50, which could be abolished by overexpression of PAX6. On the other hand, knocking down miR-223 in GBM cells with antagomir significantly enhanced the inhibitory effect of TMZ on GBM cell proliferation and decreased the TMZ IC50, which could be abolished by knockdown of PAX6. In conclusion, the present study demonstrated that TMZ inhibits GBM cell proliferation by inhibiting the expression of miR-223, which leads to increased expression of tumor suppressor PAX6. Overexpression of miR-223 increases TMZ chemoresistance, while inhibition of miR-223 with antagomir markedly decreases TMZ chemoresistance in GBM cells. The present study provided novel insight into the molecular mechanisms underlying the pharmacological effects, in addition to the chemoresistance, of TMZ for GBM.

Macrophages can be polarized into the inflammatory M1 lineage or the immunomodulatory M2 lineage, depending on the differential tissue microenvironment signaling, specific pathogens or cytokine stimulation. Tumor necrosis factor α‑induced protein 8‑like protein 2 (TIPE2) has been demonstrated to negatively regulate inflammation by inhibiting the Toll‑like receptor (TLR) pathway. The present study utilized murine bone marrow derived macrophages (BMDMs) as the model of undifferentiated (M0) macrophages to study the roles of TIPE2 in the differential polarization status of BMDMs. It was observed that the expression levels of TIPE2 were diminished in M1 macrophages treated with lipopolysaccharide/interferon γ, and elevated in M2 macrophages treated with interleukin (IL)‑4. BMDMs with TIPE2 overexpression exhibited defective M1 polarization and enhanced responses to IL‑4 stimulation. TIPE2 impeded M1 polarization by interfering with mitogen‑activated protein kinase kinase kinase 7‑inhibitor of nuclear factor‑κB kinase subunit β and B cell receptor‑associated protein‑serine/threonine‑protein kinase mTOR complex 1 (mTORC1) activation. TIPE2 overexpression accelerated IL‑4 induced M2 polarization by dampening mTORC1 activation via the accelerated process of arginine to urea. Overall, these results define a key role for TIPE2 in macrophage polarization by impeding mTORC1 response.

MicroRNAs (miRNAs) have been demonstrated to be important in the development and progression of various types of cancer. However, the exact roles of certain anti‑oncogenic miRNAs in human malignant gliomas remain to be elucidated. The present study aimed to reveal the expression of microRNA‑203 (miR-203) in normal brain tissues and gliomas, and to investigate the role of miR-203 in cell proliferation and migration in human glioblastoma U251 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of miR-203 in high WHO grade glioma tissues was significantly decreased compared with low WHO grade glioma tissues and normal brain tissues, and its expression demonstrated a decreasing tendency with ascending WHO grades. The transfection of the miR-203 mimic into U251 cells markedly downregulated the expression of phospholipase D2 (PLD2), which was identified as a direct target of miR-203. Furthermore, miR-203 overexpression significantly suppressed the proliferation and invasion of U251 cells, while the overexpression of PLD2 abrogated these effects induced by the miR-203 mimic. In conclusion, the present study demonstrated the clinical significance of miR-203 in gliomas and suggested that miR-203 was able to inhibit the proliferation and invasion of glioma cells, partially at least via suppressing the protein expression of PLD2. Thus, miR-203 may be a novel candidate for the development of therapeutic strategies for gliomas.

The aim of the present study was to identify key genes that may be involved in the pathogenesis of Tetralogy of Fallot (TOF) using bioinformatics methods. The GSE26125 microarray dataset, which includes cardiovascular tissue samples derived from 16 children with TOF and five healthy age‑matched control infants, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed between TOF and control samples to identify differentially expressed genes (DEGs) using Student's t‑test, and the R/limma package, with a log2 fold‑change of >2 and a false discovery rate of

Malignant glioma is the most common type of cancer in the central nervous system, with highly invasive characteristics. The Rho-associated protein kinase (ROCK1) has been found to act as key regulator of actin cytoskeleton reorganization, a process closely associated with cancer cell invasion. microRNA-145 (miRNA-145) has been recently shown to act as a suppressor in several types of tumor, including glioma. However, the exact regulatory mechanism by which miR-145 inhibits glioma still remains to be uncovered. In this study, we report that the miR-145 level was significantly reduced in glioma tissues and in the human glioma cell lines U87 and U251, as compared to matched adjacent and normal brain tissues. We then identified the ROCK1 gene as a novel target of miR-145. The expression of ROCK1 was markedly upregulated in glioma tissues, as well as in U87 and U251 cells. Moreover, miR-145 significantly inhibited ROCK1 protein expression in U87 cells. We further show that miR-145 transfection considerably reduced the invasive ability of U87 cells, and was accompanied by the downregulation of matrix metalloproteinase 2 and 9, an effect which could be attenuated by overexpression of ROCK1. In conclusion, the present study suggests that miR-145 can inhibit U87 glioma cell invasion, at least partially via downregulation of the RhoA/ROCK1 pathway. In conclusion, this is the first study to report that ROCK1, as a novel target of miR-145, acts as a positive regulator of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for glioma treatment.

In this study, the role of the endothelin B receptor (ETBR) in oligodendroglioma cell proliferation and survival was investigated in vitro and in vivo. The overexpression and knockdown of ETBR was conducted in Hs683 human oligodendroglioma cells, and cell proliferation and activation (phosphorylation) of extracellular signal-regulated kinase (ERK) were measured in vitro. An orthotopic xenograft oligodendroglioma mouse model was established. Mouse survival times and immunohistochemical Ki67 staining in the xenografts were examined. In vitro experiments demonstrated that the overexpression of ETBR significantly enhanced the proliferation of oligodendroglioma cells and the activation of ERK compared with the controls, which was eliminated by the selective ETBR inhibitor BQ788 and ERK-specific inhibitor U0126, but not selective endothelin A receptor inhibitor BQ123. By contrast, the knockdown of endogenous ETBR markedly decreased oligodendroglioma cell proliferation and the activa- tion of ERK compared with the controls. Overexpression of ETBR significantly increased immunohistochemical Ki67 staining in the Hs683 cell orthotopic xenograft and decreased animal survival. By contrast, knockdown of ETBR signifi - cantly decreased Ki67 staining and increased mouse survival times. Intratumoral injection of BQ788, but not BQ123, signifi - cantly decreased Ki67 staining and prolonged mouse survival times. In conclusion, ETBR was demonstrated to mediate the proliferation of oligodendroglioma cells according to an ERK-dependent mechanism. Using an orthotopic xenograft oligodendroglioma mouse model, it was demonstrated in vivo that ETBR promotes oligodendroglioma proliferation and that the selective ETBR antagonist effectively inhibits the prolifer- ation of oligodendroglioma cells and prolongs survival times. This study provides a novel insight into the role of ETBR in oligodendroglioma proliferation and survival, and provides the first in vivo evidence that ETBR-specific antagonists are a potential therapeutic alternative for oligodendrogliomas.