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MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue. Transfection of miR-548c-3p inhibited cell proliferation by inducing G1 cell cycle arrest and also inhibited the migration of the T98G cells in vitro. Furthermore, a bioinformatic algorithm and a luciferase reporter assay identified proto-oncogene c-Myb (c-Myb) as a potential direct target of miR-548c-3p. Further experiments demonstrated that the inhibition of c-Myb by miR-548c-3p partially mediated the antitumor effect of miR-548c-3p. The results of the present study provide the novel insight that miR-548c-3p inhibits glioma tumorigenesis by targeting c-Myb. Therefore, miR-548c-3p may contribute to the development of improved glioma treatment. [ABSTRACT FROM AUTHOR]

A component purified from Strongylocentrotus nudus eggs on a diethylaminoethyl cellulose-52 chromatography column and eluted using a NaCl solution gradient (SEP-S), is a homogeneous polysaccharide of α-D-glucan with a reduced molecular weight of 9.33x105 Da, compared with that of S. nudus egg polysaccharide (SEP). In an in vivo antitumor assay of histocompatibility-22 hepatocellular carcinoma in tumor-bearing mice, the inhibitory rates at SEP-S doses of 5, 10 and 20 mg/kg/day were 38.8, 50.7 and 70.3%, respectively. In addition, the spleen and thymus indices and the percentages of cluster of differentiation (CD) 4+ and CD8+ T cells were significantly increased, and the activity of cytotoxic T lymphocytes was notably enhanced, suggesting that the anti-hepatocellular carcinoma activity is mediated by boosting the immune system. In vitro experiments also demonstrated that splenocyte proliferation induced by SEP-S was inhibited by the toll-like receptor (TLR) 2 and TLR4 monoclonal antibodies. These data indicate that SEP-S is a polysaccharide component possessing high anti-hepatocellular carcinoma activity and may be a potential immunotherapy candidate for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second most common malignancy in women worldwide and always has recurrence owing to radioresistance. MicroRNA (miRNA or miR) has been identified to relate to the sensitivity of cancer radiotherapy. Here, we investigated the potential of miRNA-320 as a biomarker for radiosensitivity by targeting β-catenin in cervical cancer. A radioresistant cervical cancer cell line, C33AR, was established, and the radioresistance of C33AR cells was confirmed by a colony-formation assay. The expression of miRNA-320 was detected by reverse transcription-quantitative polymerase chain reaction, and compared between C33A and C33AR. β-catenin, the target of miRNA-320, was determined at the protein level by western blotting after transfecting the inhibitor of miRNA-320. The expression of miRNA-320 was markedly decreased in C33AR cells, which appeared to be more radioresistant, compared with its parental cell line C33A. Target prediction suggested that miRNA-320 negatively regulated the expression of β-catenin. Knockdown of β-catenin increased C33AR radiosensitivity, which revealed that the inhibition of β-catenin could rescue the miRNA-320-mediated cell radioresistance. On the other hand, overexpressing miRNA-320 increased C33AR radiosensitivity. In conclusion, miRNA-320 regulated the radiosensitivity of C33AR cells by targeting β-catenin. This finding provides evidence that miRNA-320 may be a potential biomarker of radiosensitivity in cervical cancer. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the PAQR3 gene expression and its methylation level in colorectal cancer tissues, as well as the association with colorectal cancer clinical data. In total, 54 cases of colorectal cancer tissue samples and normal adjacent tissue samples were collected between June, 2013 and July, 2014. RT-PCR and western blot analysis were used to detect the mRNA and protein levels of PAQR3 in colorectal samples, respectively. MSP was used to detect the methylation level of PAQR3 gene in colorectal samples, which was compared with colorectal data. The results showed that a decreased expression level of PAQR3 mRNA in colorectal cancer tissues and the expression reduction rate was 57.4% (31/54). Similarly, the expression level of PAQR3 protein was reduced in cancer tissues, and the reduction rate was 46.3% (25/54), while the protein expression reduction rate in cancer adjacent tissue was 5.6% (3/54), and the difference was statistically significant (P<0.05). Furthermore, the methylation rates of PAQR3 in cancer tissues and cancer adjacent tissues were 33.3% (18/54) and 5.6% (3/54), respectively. In addition, PAQR3 mRNA and protein levels in colorectal cancer tissues were associated with the differentiation degree, lymphatic metastasis and tumor infiltration depth. The methylation level of PAQR3 was associated with age, differentiated degree, lymphatic metastasis and tumor infiltration depth. In conclusion, the expression of PAQR3 mRNA and protein in colorectal cancer was reduced and methylation of PAQR3 occurred. Although the PAQR3 mRNA and protein levels were not associated with gender, age or the location of tumor, there was an association with differentiation degree, lymphatic metastasis and tumor infiltration depth. In addition, the methylation level of PAQR3 was not correlated with gender or tumor location, but was correlated with age, differentiation degree, lymphatic metastasis and tumor infiltration depth. [ABSTRACT FROM AUTHOR]

Immunotherapy with tumor lysate-pulsed dendritic cells (DCs) is one of the breakthrough strategies used in the treatment of cancer. However, DC-based immunotherapies for osteosarcoma are limited. In the present study, preclinical studies of a C3H osteosarcoma mouse model (produced by subcutaneous injection of LM8 murine osteosarcoma cells) validated the concept that LM8 cell lysate-pulsed bone marrow-derived DCs may evoke a more potent immune response compared with DCs that have been matured using polyinosinic:polycytidylic acid (poly I:C). A cytotoxic T lymphocyte (CTL) response was established using two groups of C3H mice (n=9) with osteosarcoma; the treatment group consisted of LM8 cell lysate-pulsed DCs and the control group consisted of DCs matured using poly I:C. Each group was immunized with doses of 1x106 cells twice per week for 3 weeks. No difference in the expression of cluster of differentiation markers was identified in the two groups. DCs pulsed with LM8 cell lysate were associated with the increased induction of CTL activity. Serum interferon-γ levels were increased in mice that received DCs pulsed with LM8 cell lysate compared with that in the poly I:C-matured DC group (P<0.041). Serum interleukin-4 was decreased in the treatment group vs. the control group (P<0.033). A mixed lymphocyte reaction assay confirmed that LM8-DC immunotherapy may evoke a significant antigen-specific immune response in a mouse model. The present study reveals promising data on efficacy of a DC-based immunotherapy in the treatment of osteosarcoma; however, further clinical studies are warranted. [ABSTRACT FROM AUTHOR]

The present study aimed to identify the factors involved in the resistance to endocrine therapy in breast cancer (BC) patients with a positive estrogen receptor status via the collection of clinical, pathological and immunohistochemical indices. A retrospective survey was performed in patients who experienced the relapse and metastasis of BC between November 2007 and March 2013. A total of 45 patients were enrolled, and the observational duration was 7-84 months. The Kaplan-Meier method was used to create a survival curve, while the log-rank test was used to analyze the survival curve and the Cox regression analysis was used to investigate the associated factors contributing to the resistance to endocrine therapy. Univariate analysis showed that the age of onset, the use of radiotherapy, the endocrine treatment program, and the expression levels of progesterone receptor (PR) and CerbB2 affected the impact of endocrine treatment. The Cox regression analysis indicated that the age of onset, the use of radiotherapy, and the expression levels of PR and CerbB2 affected the disease-free survival time after endocrine therapy. A young age of onset, not receiving radiotherapy, a low expression level of PR and a high expression level of CerbB2 were the risk factors involved in the resistance to endocrine therapy in patients with BC. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. Given that pigment epithelium-derived factor (PEDF) inhibits angiogenesis, the present study analyzed whether PEDF expression is associated with EMT and prognosis in invasive ductal breast cancer (IDC). Immunohistochemical analysis was used to examine the expression levels of PEDF, E-cadherin, vimentin, Snail and nuclear factor-κB (NF-κB) in 119 cases of IDC. Correlations between PEDF expression and EMT-related genes, and clinicopathological features and clinical prognosis were analyzed. E-cadherin, vimentin, Snail and NF-κB expression was correlated with tumor size, lymph node metastasis and clinicopathological stage. PEDF expression was closely associated with tumor size. Spearman's rank correlation analysis revealed a positive correlation between PEDF and E-cadherin, vimentin, Snail and NF-κB expression (P<0.05). Additionally, Kaplan-Meier survival analysis demonstrated that the five-year survival rate was higher for patients with PEDF-.and E-cadherin-positive tumors, but was lower for those with vimentin-, Snail- and NF-κB-positive tumors. Vimentin, E-cadherin and NF-κB levels were dependent prognostic factors of favorable outcomes in IDC, as determined by Cox multivariate analysis. PEDF expression in breast cancer was significantly associated with EMT-related genes, suggesting that it may be an EMT suppressor. However, its potential as a prognostic indicator in breast cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

Peroxiredoxin 1 (Prx1) has a significant role in several malignant types of tumor. However, the role of Prx1 in oral leukoplakia (OLK) has remained to be elucidated. OLK is a common precancerous lesion of the oral mucosa that has a very high malignant transformation rate. The aim of the present study was to investigate the roles of Prx1, and its association with apoptosis signal-regulating kinase 1 (ASK1) and p38 in OLK. A total of 20 OLK samples and 10 normal oral mucosa samples were obtained from patients at the Beijing Stomatological Hospital (Beijing, China). The messenger RNA (mRNA) and protein expression levels of Prx1, ASK1 and p38 were determined by polymerase chain reaction and western blot analysis, respectively. Flow cytometry was used to detect cell apoptosis. The interaction between Prx1 and ASK1 was examined in H2O2-treated DOK cells by glutathione-S-transferase pull-down assays and by co-immunoprecipitation in vitro. Compared with those of the normal oral mucosa, the mRNA levels of Prx1, ASK1 and p38 were elevated in OLK tissues (P<0.05). The protein expression levels of Prx1, phosphorylated-ASK1 (p-ASK1) and p-p38 were also significantly enhanced in OLK tissues compared with those of the normal mucosa (P<0.05). In Prx1-knockdown DOK cells, ASK1 and p38 were activated, leading to enhanced levels of apoptosis in response to H2O2. No clear interaction between Prx1 and ASK1 was detected in H2O2-treated DOK cells. Prx1 was suggested to be involved in OLK pathogenesis by providing resistance against extracellular damages from oxidative stress via inhibition of the ASK1-induced apoptotic signaling pathway. Targeting Prx1 may provide a novel therapeutic strategy for the treatment of patients with OLK. [ABSTRACT FROM AUTHOR]

Protein-tyrosine phosphatase SHP2 is encoded by the gene PTPN11. SHP2 is hypothesized to have a critical role in cancer, via the activation of mutations that have been detected in several types of leukaemia and in certain solid tumours, including liver, breast, gastric and cervical cancer. However, to the best of our knowledge, there have been no previous reports evaluating the significance of SHP2 expression in thyroid cancer. The present study evaluated SHP2 expression in 65 thyroid cancer specimens, 40 specimens of self-matched adjacent peritumour tissues and 40 specimens of normal thyroid tissue, using immunohistochemical and western blot analyses with an anti-SHP2 antibody. Western blotting was also used to assess SHP2 expression in thyroid cancer cell lines (SW579, IHH-4, FTC-133, TPC-1, DRO, TA-K, and ML-1) and Nthy-ori3-1 normal thyroid cells. In addition, SHP2 antisense oligonucleotides were used to block SHP2 expression in SW579 cells, and growth inhibition assays were conducted. Increased SHP2 expression was detected in the tumour tissues compared with that of the normal thyroid tissues (P<0.05). SHP2 expression was significantly correlated with poor tumour differentiation (P<0.05), late TNM stage (P<0.05) and lymph node metastasis (P<0.05), suggesting that SHP2 may represent a potential target for thyroid cancer therapy. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the role of PTCH1 methylation in gastric carcinogenesis and the therapeutic effect of the methylation inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), in the treatment of gastric cancer. Total RNA was extracted from 20 gastric cancer tissues, their corresponding adjacent normal tissues and a gastric cancer AGS cell line. PTCH1 mRNA expression was detected by quantitative PCR, and the PTCH1 methylation of the promoter was examined by methylation-specific PCR. The AGS cells were treated with 5-Aza-dC; apoptosis and the cell cycle were examined by flow cytometry, and the PTCH1 methylation level was observed. PTCH1 expression was negatively correlated with promoter methylation in the gastric cancer tissues, their corresponding adjacent normal tissues and the gastric cancer AGS cell line (r=-0.591, P=0.006). 5-Aza-dC treatment caused apoptosis and the G0/G1 phase arrest of the AGS cells, and also induced the demethylation and increased expression of PTCH1. In conclusion, the study found that the hypermethylation of the PTCH1 gene promoter region is one of the main causes of low PTCH1 expression in AGS cells. Demethylation agent 5-Aza-dC can reverse the methylation status of PTCH1 and regulate the expression of PTCH1, indicating its potential role in gastric cancer treatment. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common types of cancer in females worldwide, and metastasis to bone is an important characteristic of malignancy. The present study aimed to investigate the molecular mechanism of breast cancer to bone metastasis of secreted protein acidic and rich in cysteine (SPARC). Immunohistochemistry was performed to examine the expression of SPARC in primary breast tumors and bone metastatic foci. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression level of SPARC in several types of breast cancer cell. A Transwell filter assay was used to assess the effect of SPARC on breast cancer cell invasion ability, and an osteoblast differentiation assay was employed to analyze the effect of SPARC on the differentiation ability of mesenchymal stem cells. Clinical data revealed that decreased stromal SPARC expression is associated with breast cancer to bone metastasis. Gain- and loss-of-function studies reveal that SPARC inhibits the migration and invasion of breast cancer cells, and suppresses osteoclast activation in the breast cancer microenvironment. SPARC serves an important role in breast cancer bone metastasis and may be a promising therapeutic target for the treatment of breast cancer bone metastasis. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC. [ABSTRACT FROM AUTHOR]

Peroxiredoxin 1 (Prx1) is important in the protection of cells from oxidative damage and the regulation of cell proliferation and apoptosis. Prx1 is overexpressed in oral precancerous lesions of oral leukoplakia (OLK) and oral cancer; however, the association between Prx1 expression and OLK pathogenesis remains unknown. The present study investigated the role of Prx1 and its molecular mechanisms in oxidative stress-induced apoptosis during the pathogenesis of OLK. Wild-type and Prx1 knockout mice were treated with 50 μg/ml 4-nitroquinoline-1-oxide (4NQO) or 4NQO + H2O2 for 16 weeks to establish mouse models with tongue precancerous lesions. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The expression of Prx1, apoptosis signal-regulating kinase 1 (ASK1), phosphor-ASK1, p38 and phosphor-p38 was analyzed using immunohistochemical staining, and their mRNA expression levels were evaluated by reverse transcription quantitative polymerase chain reaction. The present results demonstrated that 4NQO or 4NQO + H2O2 induced the development of tongue precancerous lesions in Prx1 knockout and wild-type mice. Prx1 was overexpressed in tongue precancerous lesions compared with normal tongue mucosa. There was a significant decrease in the degree of moderate or severe epithelial dysplasia, and mild epithelial dysplasia was clearly elevated, in Prx1 knockout mice treated with 4NQO + H2O2 compared with wild-type mice treated with 4NQO + H2O2. Prx1 suppressed apoptosis and upregulated phosphor-ASK1 and phosphor-p38 expression in tongue precancerous lesions. The present results suggest that Prx1 suppresses oxidative stress-induced apoptosis via the ASK1/p38 signalling pathway in mouse tongue precancerous lesions. In conclusion, Prx1 and H2O2 have a coordination role in promoting the progression of tongue precancerous mucosa lesions. The present findings provide novel insight into Prx1 function and the mechanisms of Prx1 in OLK pathogenesis. [ABSTRACT FROM AUTHOR]

The association between hepatocellular carcinoma (HCC) and the epidermal growth factor (EGF) 61A/G polymorphism has been analyzed in several studies, but results remain inconsistent. Therefore, the aim of the present study was to quantitatively summarize the association between the EGF 61A/G polymorphism and the risk of HCC. The PubMed and EMBASE databases were searched for studies published prior to May 1, 2014. The overall, subgroup and sensitivity analyses were conducted using Comprehensive Meta-Analysis software, version 2.2. In total, 12 published case-control studies, consisting of 2,095 patients with HCC and 3,766 control individuals, were included in the present study. Meta-analysis of the included studies revealed that EGF 61A/G polymorphism contributed to the risk of HCC under all four genetic models, consisting of the G vs. A (OR, 1.25; 95% CI, 1.11-1.40), GG vs. AA (OR, 1.53; 95% CI, 1.26-1.85), GG vs. AG + AA (OR, 1.34; 95% CI, 1.13-1.58) and GG + AG vs. AA (OR, 1.27; 95% CI, 1.08-1.49) comparisons. Subgroup analysis further suggested that EGF 61A/G polymorphism was associated with the risk of HCC in patients and control individuals with liver disease, based on ethnicity and source of control, respectively. No other significance in residual subgroup analysis was observed. The present meta-analysis suggests that the EGF 61A/G polymorphism is associated with an increased risk of HCC and may be a potential marker for liver disease, such as hepatitis B virus infection, hepatitis C virus infection and liver cirrhosis. [ABSTRACT FROM AUTHOR]