Interleukin-6 released by oral lichen planus myofibroblasts promotes angiogenesis.

Oral lichen planus (OLP), defined as a potential for malignant transformation, is a chronic inflammatory disease in which abnormal angiogenesis serves a role in the malignant changes of the disease. OLP-associated fibroblasts (OLP-MFs), derived from the stroma of OLP tissues, are characterized by the presence of myofibroblasts and contribute to the secretion of pro-inflammatory cytokines, which may be involved in the molecular pathogenesis of OLP. However, the associated mechanisms of angiogenesis in OLP remain unknown. The present study aimed to verify the expression of intercellular adhesion molecular 1, vascular cell adhesion molecule 1, VEGF and CD34 in OLP, and to investigate whether IL-6 secreted by OLP-MFs promoted OLP angiogenesis and the effect of its corresponding antibody inhibition. The results of the experiments demonstrated that inflammation was present and OLP upregulated the secretion of IL-6 by OLP stromal fibroblasts, thereby enhancing OLP angiogenesis. Anti-IL-6 receptor antibody inhibited OLP-stroma IL-6 signaling and suppressed OLP angiogenesis. The antibody inhibited the inflammatory response by inhibiting the secretion of inflammatory factors, including IL-6, to suppress angiogenesis and reduce disease progression, thus indicating that this could be a potential target to develop a treatment for OLP.

TSP2 acts as a suppresser of cell invasion, migration and angiogenesis in medulloblastoma by inhibiting the Notch signaling pathway.

Medulloblastoma (MB) represents a fatal malignancy often occurring in children. Angiogenesis is a hallmark of the progression of MB. Over the past decade, investigators have attempted to develop more effective and less toxic anti-angiogenic strategies to treat MB. Thrombospondin (TSP) family is observed to be a key regulator of angiogenesis. Thus, the current study aimed to elucidate the function of TSP2 in patients with MB and the underlying mechanism. The expression of TSP2, Notch1 and VEGF in MB and adjacent tissues collected from clinical samples as well as a MB cell line (Daoy) was examined. The results demonstrated that in the MB tissues and Daoy cells, TSP2 was downregulated, while Notch1 and VEGF were upregulated. Then, after the Daoy cells were treated with TSP2 silencing, TSP2 overexpression, or Notch signaling pathway inhibition, a series of in vitro cell experiments were performed to verify the interaction between TSP2 and Notch signaling pathway, and to examine the abilities of cell proliferation, migration, invasion, and tube formation. Upregulation of TSP2 was observed to lead to the downregulation of the Notch signaling pathway. Moreover, cells overexpressing TSP2 exhibited diminished proliferation, invasion, migration, and tube formation. In addition, a significant attenuation of tumor growth and angiogenesis was identified in vivo in the Daoy cells overexpressing TSP2 inoculated in nude mice. Taken together, the key findings of this study revealed the inhibitory role of TSP2 in the development of MB via blockade of the Notch signaling pathway, highlighting its potential as a treatment target for MB treatment.

Retracted: Effects of microRNA-494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c-myc through the p38 MAPK signaling pathway.

Medulloblastoma (MB) is the most prevalent brain tumor that occurs during childhood and originates from cerebellar granule cell precursors. Based on recent studies, the differential expression of several microRNAs is involved in MB, while the role of microRNA-494 (miR-494) in MB remains unclear. Therefore, we conducted this study to investigate the regulative role of miR-494 in MB cells via the p38 mitogen-activated protein kinase (MAPK) signaling pathway by mediating c-myc. In the current study, MB cells were collected and transfected with miR-494 mimic, miR-494 inhibitor, siRNA- c-myc, and miR-494 inhibitor + siRNA-c-myc. The expressions of miR-494, c-myc, p38 MAPK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), interleukin-6 (IL-6), metadherin (MTDH), phosphatase and tensin homolog (PTEN) and survivin were determined. Cell proliferation, cell-cycle distribution, apoptosis, migration, and invasion were evaluated. The results revealed that there was a poor expression of miR-494 and high expression of c-myc in MB tissues. C-myc was determined as the target gene of miR-494. In response to miR-494 mimic, MB cells were found to have increased Bax and PTEN expressions, as well as cell number in G1 phase and cell apoptosis and decreased c-myc, p38 MAPK, Bcl-2, MTDH, IL-6, and survivin expression and cell number count in the S phase, cell proliferation, migration, and invasion. In conclusion, the results demonstrated that the upregulation of miR-494 results in the suppression of cell proliferation, migration, and invasion, while it promotes apoptosis of MB cells through the negative mediation of c-myc, which in turn inactivates the p38 MAPK pathway.

[Clinical characteristics and gene mutation analysis of one pedigree with infantile glycogen storage disease type II].

The clinical data of 2 infants with infantile glycogen storage disease type II (GSD II) from one pedigree were collected. The method of dried blood spots (DBS) was applied to collect peripheral blood samples, and the activity of acid alpha-D-glucosidase (GAA) in leukocytes was measured. The coding region of GAA gene in this pedigree was amplified by polymerase chain reaction and then direct sequencing was used to analyze mutations in GAA gene. The two infants were twins, who were admitted to the hospital due to feeding difficulties, generalized muscle weakness and hypotonia, cardiomegaly, and cardiac insufficiency when they were 10 months old. The GAA activity in leukocytes in the two infants was significantly lower than in normal controls. Gene sequencing revealed 2 compound heterozygous mutations in the two infants, i.e., G1942A and G2214A, respectively. G1942A had been proved pathogenic, and the latter one, G2214A, was a nonsense mutation, resulting in the change of tryptophan, the 738th amino acid of GAA, into a stop codon. The two infants were diagnosed with GSD II by gene detection and no enzyme replacement therapy could be provided to them. Follow-up visits showed that the two infants died at home at the age of 15 months and 17 months, respectively. GSD II is caused by deficiency of GAA activity resulting from mutation of GAA gene. The detection of GAA activity in peripheral blood by DBS and GAA gene detection are effective and feasible methods for diagnosis of GSD II.

MiR-300 regulate the malignancy of breast cancer by targeting p53.

OBJECTIVE: In this study, we investigated the role of miR-300 in regulating cell proliferation and invasion of breast cancer (BC) cells. METHODS: MicroRNA and protein expression patterns were compared between breast cancer tissue and normal tissue and between two different prognostic groups. The up-regulation of miR-300 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in MCF-7 breast cancer cells. RESULTS: We observed that miR-300 expression was frequently and dramatically up-regulated in human breast cancer tissues and cell lines compared with the matched adjacent normal tissues and cells. We further showed that transient and stable over-expression of miR-300 could promote cell proliferation and cell cycle progression. Moreover, p53, a key inhibitor of cell cycle, was verified as a direct target of miR-300, suggesting that miR-300 might promote breast cancer cell proliferation and invasion by regulating p53 expression. CONCLUSION: Our findings indicated that miR-300 up-regulation might exert some sort of antagonistic function by targeting p53 in breast cancer cell proliferation during breast tumorigenesis.

Association of annexin A2 with cancer development (Review).

Annexin A2 (ANXA2) is a well-known calcium-dependent phospholipid binding protein widely distributed in the nucleus, cytoplasm and extracellular surface of various eukaryotic cells. It has been recognized as a pleiotropic protein affecting a wide range of molecular and cellular processes. Dysregulation and abnormal expression of ANXA2 are linked to a large number of prevalent diseases, including autoimmune and neurodegenerative disease, antiphospholipid syndrome, inflammation, diabetes mellitus and a series of cancers. Accumulating data suggest that ANXA2 is aberrantly expressed in a wide spectrum of cancers, and exerts profound effects on tumor cell adhesion, proliferation, apoptosis, invasion and metastasis as well as tumor neovascularization via different modes of action. However, despite significant research, our knowledge of the mechanism by which ANXA2 participates in cancer development remains fragmented. The present review systematically summarizes the effects of ANXA2 on tumor progression, in an attempt to gain an improved understanding of the underlying mechanisms and to provide a potential effective target for cancer therapy.