Abstract. Raf kinase inhibitory protein (RKIP) regulates multiple cellular processes, and its downregulation is associated with distinct human cancers. In the present study, the status of RKIP promoter methylation, as well as its expression and clinical significance in esophageal squamous cell carcinoma (ESCC), were examined. The promoter methylation status in the 5'-CpG island of the RKIP gene and the expression level of the RKIP protein were examined using a modified methylation-specific polymerase chain reaction (MSP) method and immunohistochemical staining, respectively, in 77 ESCC samples and matched paratumor normal tissues. The incidence of RKIP promoter methylation was significantly higher in tumor samples (75.3%) than in the matched normal tissues (27.3%; P<0.001). A higher incidence of promoter methylation was also detected in poorly differentiated cancers (93.5%) compared with well-differentiated cancers (50.0%; P<0.001), as well as in tumor samples with positive lymph node metastasis (86.7%) compared with those with negative lymph node metastasis (59.4%; P<0.001). Consistent with the promoter methylation status, the expression level of RKIP was significantly reduced in cancer tissues (36.4%) compared with matched normal tissues (76.6%; P<0.01), as well as in cancers with positive lymph node metastasis (24.4%) compared with those with negative lymph node metastasis (53.1%; P=0.01). Promoter methylation-induced gene silencing significantly correlated with the down regulation of RKIP and the development of ESCC. The results of the present study suggested that the methylation status of the RKIP promoter, when combined with its expression level, may serve as a biomarker for predicting the biological behaviors of ESCC.

Long non-coding RNAs (lncRNAs) are hypothesized to regulate numerous biological behaviors in human cancers. The present study aimed to explore the roles of lncRNA bladder cancer associated transcript 1 (BLACAT1) in glioma. The expression of BLACAT1 in glioma tissues and cell lines was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). CCK-8 assay, colony formation assay, wound healing assay and Transwell invasion assay were used to explore the roles of BLACAT1 in glioma cells. RT-qPCR and western blot analysis were used to determine the BLACAT1 molecular mechanism. The findings demonstrated that lncRNA BLACAT1 was overexpressed in glioma tissues and cell lines. High BLACAT1 expression was correlated with high tumor grade in glioma patients. Functional assays determined that BLACAT1 promoted glioma cell proliferation, migration, invasion and epithelial-mesenchymal transition in vitro. In addition, it was demonstrated that BLACAT1 activated the Wnt/β-catenin signaling pathway. In conclusion, BLACAT1 may serve as an oncogenic lncRNA in glioma progression via activation of the Wnt/β-catenin signaling pathway. Therefore, BLACAT1 may be a novel therapeutic target for glioma treatment.

A novel magnetic-targeted pH-responsive intelligent drug carrier based on hollow mesoporous structured NiFe2O4 nanospheres was designed and developed for potential anticancer treatment in the present study. The hollow mesoporous NiFe2O4 nanospheres were fabricated through a template-free solvothermal approach and the possible formation mechanism of this structure was proposed. The products were investigated comprehensively for their morphology, microstructure, composition and magnetic properties using a wide series of characterization methods. The NiFe2O4 nanospheres were demonstrated to possess a well-defined spherical morphology, homogeneous particle size distribution, large hollow cavities and abundant mesopores, unique superparamagnetic behavior, high saturation magnetization as well as good biocompatibility. Due to these desirable physicochemical properties, the hollow mesoporous NiFe2O4 nanospheres were expected to be employed as a potential vehicle for loading and delivering anticancer drug of doxorubicin hydrochloride (DOX). Drug release behavior was evidenced to be controllable and pH-responsive with effective DOX release of 73.1% and 58.8% in acidic conditions (pH 4.0 and 5.5), whereas insufficient drug release of 44.7% at a neutral atmosphere (pH 7.4) within 48 h. More importantly, the DOX-loaded NiFe2O4 nanospheres displayed significant anti-proliferation and apoptosis effects on human breast cancer cells (MCF-7), which further indicated the promising potential application of constructed drug delivery nanocarriers in the field of cancer therapy.