Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic

Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer

Introduction: Tumor growth depends on intrinsic properties of malignant tumor and tumor microenvironment. Cytokines are secreted substances of the tumor microenvironment which are widely produced by tumor and immune cells. The aim of this research was to evaluate concentrations of interleukin 4 (IL-4), interleukin 7 (IL-17) and interferon gamma (IFN-γ) in the breast cancer microenvironment. Methods: One hundred sixteen women between 18-73 years of age (61.15 ± 24.39) were enrolled in this study. Based on pathologic diagnostic assessment, patients were divided into 2 categories: those affected with benign breast tumor, and the subjects suffering from malignant breast tumors. Biopsy specimens were collected. Following homogenization, IFN-γ, IL-17, and IL-4 concentrations were determined in tumor tissues, adjacent tissues of the tumor, and blood serum samples of these 2 groups of patients by enzyme-linked immunosorbent assay (ELISA) method. Results: Concentrations of IFN-γ, IL-17, and IL-4 were measured in tumor tissue samples, adjacent tissues of the tumor, and blood serum samples in both groups. Malignant breast tumor samples had significantly higher concentrations of IL-4 and IL-17 compared with benign breast tumor samples. And also the concentration of IFN-γ in adjacent tissues of the tumor and in blood serums in patients with malignant breast tumors was significantly higher than that in the benign breast tumor samples. However, there was no significant difference between the concentration of IFN-γ in neoplastic breast tumor tissues and that in the benign breast tumor tissues (P > 0. 05). Conclusion: Our data indicated that IL-17 and IL-4 cytokines but not IFN-γ had higher concentrations in the subjects with malignant tumor compared with those with benign tumor. The present findings indicated that the concentrations of IL-4 and IL-17 in tumor tissues may be associated with the severity of breast malignancy

Association between indices of body mass and antibody titers to heat-shock protein-27 in healthy subjects

OBJECTIVES We have assessed the relationship between indices of adiposity and antibody titers to Hsp-27 in healthy subjects. DESIGN Two-hundred and fifty subjects were studied, including 50 normal-weight subjects (body-mass-index (BMI) 25 kg/m(2)), 100 overweight subjects (BMI 25 to 30 kg/m(2)) (n=100) and 100 obese subjects (BMI ≥ 30 kg/m(2)). RESULTS Anti-Hsp27-antibody levels in obese subjects were [0.34 (0.20-0.39) absorbency unit], being significantly higher than overweight and normal-weight groups (P<0.05). Anti-Hsp27-antibody levels in overweight subjects [0.29 (0.15-0.34) absorbency unit] were statistically higher than controls [0.18 (0.10-0.23) absorbency unit] (P<0.05). CONCLUSION High anti-Hsp-27-antibody levels in obese-subjects without established coronary disease may be related to a heightened state of immunoactivation associated with obesity

A cross-sectional study of the association between heat shock protein 27 antibody titers, pro-oxidant-antioxidant balance and metabolic syndrome in patients with angiographically-defined coronary artery disease

OBJECTIVE To investigate the association between serum antibody titers to Hsp27 (anti-Hsp27) and pro-oxidant-antioxidant balance (PAB) in patients with angiographically-defined coronary artery disease (CAD) with or without the metabolic syndrome (MS). DESIGN Subjects (n=243) were classified into MS+ (n=161) and MS- (n=82) subgroups, based on the AHA/NHBLI criteria. RESULTS Serum anti-Hsp27 titers were found to be significantly higher in the MS+ vs. MS- group. However, no significant difference was observed in serum PAB values. When assessed for individual components of MS, increased serum anti-Hsp27 was found to be higher in subgroups with elevated triglycerides, elevated blood pressure and reduced high-density lipoprotein cholesterol (HDL-C). Subgroups of patients with elevated triglycerides had higher PAB values. HDL-C was the only significant predictor of anti-Hsp27 in the population as a whole. CONCLUSION The evidence from this investigation indicates the presence of elevated anti-Hsp27 in patients with concurrent CAD and MS compared to those with CAD alone

Prooxidant-anti-oxidant balance is not associated with extent of coronary artery disease

OBJECTIVE We have measured the pro-oxidant-antioxidant-balance (PAB) levels in patients with defined coronary artery disease (CAD) and compared them with concentrations in healthy subjects. DESIGN AND METHODS Based on angiography results, 400 patients with stable CAD were divided into CAD- and CAD+, this being further subcategorized into groups with single-, double- and triple-vessel disease (VD). RESULTS The mean PAB values in the healthy subjects, was significantly lower than for other groups (P0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD were not significantly different among patients with SVD, 2VD and 3VD (P>0.05). CONCLUSIONS In conclusion, we found higher levels of oxidative stress in CAD+ patients compared to healthy subjects. The oxidation level was not related to measures of the extent of CAD such as number of stenosed vessels

Anti-heat shock protein 27 titers and oxidative stress levels are elevated in patients with valvular heart disease

We studied the immune responses to heat shock protein (Hsp)-27 and pro-oxidant-antioxidant balance (PAB) values in patients with valvular heart disease, but free of angiographically evident coronary artery disease (CAD). Patients who were candidates for valvuloplasty surgery and 30 healthy matched controls were recruited. The anti-Hsp-27 antibody titers were 0.35 ± 0.04 absorbency units (AU) in the valvuloplasty group, being significantly higher than for the controls (0.11 ± 0.02 AU; P .05). Based on the echocardiographic findings, the patients had no evident heart failure, but the high levels of anti-Hsp-27 and PAB values in patients with valvular heart disease may indicate that these variables can be used as markers of heart failure. However, a longitudinal study is required to confirm this hypothesis

Serum antibody titers against heat shock protein 27 are associated with the severity of coronary artery disease

Antibody titers to several heat shock proteins (anti-Hsps) have been reported to be associated with the severity and progression of cardiovascular disease. However, there are little data regarding anti-Hsp27 titers in patients with coronary artery disease (CAD). A total of 400 patients with suspected CAD were recruited. Based on the results of coronary angiography, these patients were classified into CAD+ (n = 300) and CAD− (n = 100) groups defined as patients with ≥50% and <50% stenosis of any major coronary artery, respectively. Eighty-three healthy subjects were also recruited as the control group. Serum anti-Hsp27 IgG titers were measured using an in-house enzyme-linked immunosorbent assay. CAD+ patients had significantly higher anti-Hsp27 titers compared with both CAD− and control groups. Anti-Hsp27 titers were also higher in the CAD− group compared with the control group. With regard to the number of affected vessels in the CAD+ group, patients with three-vessel disease had higher anti-Hsp27 titers compared with both two-vessel disease (2VD) and one-vessel disease (1VD) subgroups. However, there was no significant difference between 1VD and 2VD subgroups. In multiple linear regression analysis, the number of narrowed vessels and smoking were significant independent determinants of serum anti-Hsp27 titers. The present findings indicate that serum anti-Hsp27 titers may be associated with the presence and severity of coronary artery disease