Hypoxia induced cell dormancy of salivary adenoid cystic carcinoma through miR-922/DEC2 axis

Abstract

Background: Hypoxia has been shown to induce cancer cells to become dormant meanwhile these cells inclined to disseminate and eventually cause metastasis. However, the molecular mechanism is still elusive. The purpose is to explore whether dormancy-associated microRNAs (DmiRs) get involved in hypoxia-induced cell dormancy of salivary adenoid cystic carcinoma (SACC). Material and Methods: This study performed multi-perspective investigation of the biological effects of miR-922/DEC2 on SACC based on clinical samples, 2D and 3D in vitro model and nude mice in vivo model, based on our previous study of overexpression of DEC2 inducing SACC cellular dormancy. Results: According to the existing microRNA array of SACC tissue, we found that miR-922 was upregulated in SACC tissue and was inversely correlated with DEC2, suggesting that miR-922 might participate in the activation of SACC cell dormancy as a DmiR. Then, we found miR-922 low SACC cells exhibited cell dormancy and a low level of fatty acid oxidation with propensity for lipid droplets accumulation through DEC2. Moreover, HIF1a downregulated the level of miR-922 to induce SACC cell dormancy. In addition, in xenografts of nude mice the inhibition of miR-922 attenuated the growth of primary tumor and the lung metastasis of SACC. Conclusions: miR-922/DEC2 axis was necessary to hypoxia-induced cell dormancy and played an important role in the lipid metabolism reprogramming of SACC.

Keywords

• Salivary adenoid cystic carcinoma
• Cancer cell dormancy
• Dormancy-associated microrna
• Hypoxia