Abstract
BackgroundIntestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator.MethodsWe have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated.ResultsWe found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR-126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells.ConclusionsWe report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy.
Highlights
Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure
MiR-126 levels were significantly decreased in ITAC tissue (Fig. 1a), while MiR-126 in sinonasal-inverted papillomas (SIPs) and Nasal inflammatory polyps (NIPs) tissues were strongly increased compared to the matched normal mucosa (Fig. 1a, b)
The MiR-126 gene is located in an intron of a protein-coding gene, epidermal growth factor-like protein 7 (EGFL7), and its expression was previously reported to be closely correlated with the T2 EGFL7 transcript [21]
Summary
Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator. Cancers of the nasal cavity and the paranasal sinuses, referred to as sinonasal cancers (SNCs), are associated with occupational exposure to wood, leather and nickel particles that are reported as risk factors for the development of these tumours [1]. Around 8–25% of all SNCs are intestinal-type adenocarcinomas (ITACs), Tomasetti et al BMC Cancer (2018) 18:896. Angiogenesis is an important process in tumour progression, the vascular endothelial growth factor (VEGF) being one of the key drivers of both physiological and pathological blood vessel formation. Nasal inflammatory polyps (NIPs) include mucosal epithelial hyperplasia, infiltration of inflammatory cells, neo-vascularization, and edema [11]
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