ABSTRACT
Laryngeal cancer is one of the most malignant cancers among the head and neck malignant tumors. Abnormal expression of microRNAs (miRNAs) contributes to cancer development through regulating proliferation and apoptosis of cancer cells. In this study, we aim to explore the roles of microRNA-141 (miR-141), Homeobox C6 (HOXC6) and TGF-ß signaling pathway in epithelial-mesenchymal transition (EMT) and lymph node metastasis in laryngeal cancer. Initially, we identified differentially expressed genes in laryngeal cancer, among which HOXC6 was identified. Then the target miRNA of HOXC6 was predicted and verified. Next, expression of miR-141, HOXC6, TGF-ß1, Smad3, Vimentin and Snail in cancer tissues was detected. Then, AMC-HN-8 cells were transfected with miR-141 mimic, miR-141 inhibitor and HOXC6-siRNA to investigate specific role of miR-141, HOXC6 and TGF-ß signaling pathway in laryngeal cancer in vivo and in vitro. Our results showed that HOXC6 was a target gene of miR-141, which was downregulated in laryngeal cancer. Besides, overexpression of miR-141 could downregulate HOXC6 and inhibit the TGF-ß signaling pathway. Upregulation of miR-141 or silencing of HOXC6 can repress EMT, viability, migration and invasion abilities of laryngeal cancer cells. In addition, upregulation of miR-141 inhibited the tumor growth and lymph node metastasis in vivo. In summary, our findings demonstrated that upregulated miR-141 decreased HOXC6 expression, and inhibited the TGF-ß signaling pathway, EMT and lymph node metastasis in laryngeal cancer, which is of clinical significance in the treatment of laryngeal cancer.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Epithelial-Mesenchymal Transition , Homeodomain Proteins/metabolism , Laryngeal Neoplasms/metabolism , Lymphatic Metastasis , MicroRNAs/metabolism , Transforming Growth Factor beta1/metabolism , Aged , Animals , Apoptosis , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , Laryngeal Neoplasms/genetics , Male , Mice , Mice, Nude , Middle Aged , Signal TransductionABSTRACT
The present study aims to explore the role of stromal cell-derived factor-1α (SDF-1α)/stromal cell-derived factor receptor-4 (CXCR4) signaling pathway to the clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2009 to December 2010, 102 patients with NPC and 80 patients with chronic nasopharyngitis were enrolled for the study. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting were employed to determine the expressions of SDF-1α and CXCR4 proteins in NPC tissues and chronic nasopharyngitis tissues. Chi-square test was conducted to analyze the associations of the expressions of SDF-1α and CXCR4 proteins with the clinicopathological features of NPC patients. Spearman rank correlation analysis was used to analyze the correlation between the SDF-1α protein expression and CXCR4 protein expression. The mRNA and protein expressions of SDF-1α and CXCR4 in NPC tissues were significantly higher than those in chronic nasopharyngitis tissues. The expressions of SDF-1α and CXCR4 proteins showed associations with T staging, N staging, tumor node metastasis (TNM) staging, skull base invasion, and cervical lymph node metastasis of NPC patients. Compared with NPC patients showing negative expressions of SDF-1α and CXCR4 proteins, those with positive expressions of SDF-1α and CXCR4 proteins had a significantly shorter survival time. SDF-1α protein, CXCR4 protein, EBV-IgG status, T staging, N staging, TNM staging, skull base invasion, and cervical lymph node metastasis were independent risk factors for the prognosis of NPC. The findings indicated that SDF-1α/CXCR4 signaling pathway might be associated with the clinicopathological features and prognosis of patients with NPC.
Subject(s)
Carcinoma/metabolism , Chemokine CXCL12/biosynthesis , Gene Expression Regulation, Neoplastic , Nasopharyngeal Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Receptors, CXCR4/biosynthesis , Signal Transduction , Adult , Aged , Carcinoma/diagnosis , Carcinoma/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/pathology , PrognosisABSTRACT
An alkaline sample digestion procedure using fusion with lithium metaborate (LiBO2) after dry ashing was developed. Silicon, aluminium and other, a total of 10 elements in different kinds of biological samples, were measured by ICP-AES. The detection limit of this method was 0.15 microg x mL(-1) for Si and 0.03 microg x mL(-1) for Al. The accuracy and precision of the method were demonstrated by analyzing certified reference materials poplar leaves (GBW07604). The precision was less than 3% and the accuracy was -0.03% for Si and -3% for Al. This method was applied to the certification of a series of ten biological reference materials. The results were satisfied.
