Hypoxia-inducible factor (HIF) is a main heterodimeric transcription factor that regulates the cellular adaptive response to hypoxia by stimulating the transcription of a series of hypoxia-inducible genes. HIF is frequently upregulated in solid tumors, and the overexpression of HIF can promote tumor progression or aggressiveness by blood vessel architecture and altering cellular metabolism. In this review, we focused on the pivotal role of HIF in tumor angiogenesis and energy metabolism. Furthermore, we also emphasized the possibility of HIF pathway as a potential therapeutic target in cancer.

The purpose of this study is to explore the role of hypoxia on the invasion and metastasis of laryngeal carcinoma. The invasion and migration ability of laryngeal cancer SCC10A cell was detected by transwell assay. Western blot was applied to analyze the expression of EMT-related proteins. Fifty-seven samples from postoperative patients with laryngeal cancer were collected to study. Immunohistochemistry was used to examine the expression of GLUT-1 and EMT-related proteins (Vim, E-cad, N-cad) in normal laryngeal squamous epithelial tissue, laryngeal cancer adjacent tissues and laryngeal squamous cell carcinoma tissues. Hypoxia promoted laryngeal cancer cell invasion and migration. Hypoxia also enhanced the expression of GLUT-1, vimentin and N-cad, which exist statistically significant correlation with the clinical staging and lymph node metastases (P < 0.05). The expression of GLUT-1 is positively correlated with Vim and N-cad expression in laryngeal squamous cell carcinoma tissues, but negatively correlated with E-cad expression. The patient survival rate with the positive expression of GLUT-1, Vim and N-cad becomes much shorter compared with those with negative expression of GLUT-1, Vim and N-cad (P < 0.05). Hypoxia promoted laryngeal cancer cell invasion and migration via EMT.

The microRNA hsa-miR-210 (miR-210) is associated with hypoxia; however its function has not fully identified. In the present study, we aim to detect its role concerning proliferation in Laryngocarcinoma. We found that miR-210 was highly expressed in hypoxia, which inhibited proliferation by inducing cell cycle arrest in G1/G0 as well as apoptosis. We further identified that miR-210 targeted fibroblast growth factor receptor-like 1 (FGFRL1). Down regulation of FGFRL1 decreased cell proliferation by promoting proportion of cells in G1/G0 phase and decreasing in S and G2/M phases. Moreover, overexpression of FGFRL1 effectively released the miR-210-induced suppression of SCC10A cell proliferation. Expression of miR-210 repressed tumor xenograft growth in vivo as well. Together, our findings reveal a new mechanism of adaptation to hypoxia that miR-210 inhibits the proliferation via inducing cell cycle arrest and apoptosis by the targeting of FGFRL1. J. Cell. Biochem. 116: 1039-1049, 2015. © 2015 Wiley Periodicals, Inc.

Abstract. The aim of the present study was to verify whether overexpression of CXC receptor 4 (CXCR4) promotes the invasion and migration of non-small cell lung cancer (NSCLC) via epidermal growth factor receptor (EGFR) and matrix metallopeptidase-9 (MMP-9), and to detect the association between CXCR4, EGFR and MMP-9. The effects of overexpression of CXCR4 on lung cancer cell functions were investigated by migration and invasion assays. Western blotting and zymograph assays were used to analyze the protein expression levels of EGFR and the production of MMP-9, respectively. Immunohistochemistry was applied to analyze the expression of EGFR, CXCR4 and MMP-9 in NSCLC. Statistical analyses were used to detect the associations among EGFR, CXCR4 and MMP-9 in NSCLC. Finally, survival analyses were performed. CXCR4 overexpression enhanced cell motility and invasion. CXCR4 also promoted expression of EGFR and elevated MMP-9 production. CXCR4, EGFR and MMP-9 were highly expressed in NSCLC, and were not identified as associated with age and sex (P>0.05). However, they were associated with tumor differentiation and lymph node metastasis (P<0.05). CXCR4, EGFR and CXCR4 expression were positively associated with one another in NSCLC (P<0.05). In addition, patients with positive expression of CXCR4, EGFR or MMP-9 in tumors exhibited significantly shorter overall survival compared with those with negative expression (P<0.05). In conclusion, CXCR4 overexpression enhanced cell motility and invasion via EGFR and MMP-9. CXCR4, EGFR and MMP-9 were identified as highly expressed in NSCLC, and there was positive correlation among them.

Laryngeal carcinoma (LC) is one of the most common malignant tumors of all head and neck squamous cell carcinomas (HNSCCs). However, the molecular mechanism and genetic basis of the development of LC have not been fully elucidated. To explore the possible mechanism, targeted proteomic analysis was performed on Bcl-2-associated proteins from LC cells. According to our results, 35 proteins associated with Bcl-2 were identified and Hsp90β was confirmed by co-immunoprecipitation and western blot analysis. Protein‑protein interaction (PPI) analysis indicated that Bcl-2‑Hsp90β interactions may be involved in the anti-apoptotic progression of LC. Further results revealed that disruption of the Bcl-2-Hsp90β interaction inhibited the anti-apoptotic ability of Bcl-2 and decreased the caspase activation in LC, which has broad implications for the better understanding of tumor formation, tumor cell survival and development of metastasis due to Bcl-2. Collectively, we report the mechanism by which Bcl-2 functions in LC as an anti-apoptotic factor in relation to its association with proteins and potentially identify a Bcl-2/Hsp90β axis as a novel target for LC therapy.

Asthma is a complicated systemic disease of the airways, which is characterized by variable symptoms, including bronchial hyper‑responsive-ness, inflammation and airflow obstruction. The prevalence of asthma has increased 2‑3‑fold over recent decades in developed countries; however, the molecular mechanism of asthma remains unclear. In the current study, the expression of recombinant protein Dermatophagoides farinaeI (Derf I) was induced by isopropyl β‑D‑1‑thiogalactoside (IPTG) and purified using Ni‑NTA. Derf I, an important antigen of asthma, was used to establish the animal model of asthma. Airway hyper‑responsiveness was mea-sured using unrestrained whole‑body plethysmography with a four‑chamber system. Immunoglobulin (Ig)E, IgG and IgG2a were analyzed using indirect enzyme‑linked immunosorbent assay (ELISA). Proteomic technology was applied to detect the difference between the normal lung tissue and asthma lung tissue samples of the asthma model. Cytokines in bronchoalveolar lavage fluid and the splenocyte culture medium were measured by ELISA and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the mRNA expression of ATP synthase, H+ transporting, mitochondrial F1 complex, β polypeptide (ATP5b). In addition, cell growth of arterial smooth muscle cells (ASMCs) was evaluated by MTT assay. In the current study, Derf I was successfully used to construct the animal model of asthma. Out of 23 proteins that exhibit 3‑fold upregulation or downregulation, ATP5b was chosen for further investigation. The data indicated that ATP5b was overexpressed in the asthma lung tissue when compared with the normal lung tissue. However, when ATP5b was knocked down, cell growth decreased. Therefore, overexpressed ATP5b leads to airway smooth muscle cell (ASMC) proliferation and finally to ASM thickening. Thus, to the best of our knowledge, this is the first study to report that the expression level of ATP5b was markedly increased in lung tissue samples of an asthma model compared with the tissue samples from normal lungs, which promoted ASMC proliferation and contributed to airway remodeling.

The silkworm (Bombyx mori) can cause severe IgE-mediated allergic disease, however, the mechanism remains unclear. The aim of this study was to investigate the immunologic mechanism by which silkworms induce allergy. Whole silkworm pupa proteins were separated by SDS-PAGE and 2-D PAGE. Then, IgE-binding proteins were detected by immunoblotting with sera of patients having an allergy to Bombyx mori. After tryptic digestion, the peptides of IgE-binding proteins were analyzed by matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry or tandem mass spectrometry. Database searches were used to identify allergens in silkworm pupa, after which Bom m 9 was to construct an asthma model. Thus, in the current study, a mouse asthma model was constructed with Bom m 9.

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