This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.

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Circular RNAs (circRNAs) are involved in the development of various diseases; however, knowledge on circRNAs in osteoarthritis (OA) is limited. This study aims to identify circRNA expression in different regions affected by OA and to explore the function of mechanical stress-related circRNAs (circRNAs-MSR) in cartilage. Bioinformatics was employed to predict the interaction of circRNAs and mRNAs in the cartilage. Loss-of-function experiments for circRNAs-MSR were performed in vitro. A total of 104 circRNAs were differentially expressed in damaged versus intact cartilage. Of these circRNAs, 44 and 60 were upregulated and downregulated, respectively, in the damaged tissue. circRNA-MSR expression increased under mechanical stress in chondrocytes. circRNAs-MSR were silenced using small interfering RNA, and knockdown of circRNAs-MSR could suppress tumor necrosis factor alpha (TNF-α) expression and increase extracellular matrix (ECM) formation. Our results demonstrated that circRNAs-MSR regulated TNF-α expression and participated in the chondrocyte ECM degradation process. We propose that the inhibition of circRNAs-MSR could inhibit the degradation of chondrocyte ECM and knockdown of circRNAs-MSR could be a potential therapeutic target for OA.

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