Ceramide调控外泌体释放参与多发性骨髓瘤血管新生及其机制研究

Multiple myeloma (MM) derived exosomes play as key regulators in the maintenance and education of the BM microenvironment by targeting vascular cells. The ceramide pathway could regulate exosome secretions. Our previous study found that the ceramide pathway was involved in the survival, apoptosis and exosomal miRNA functions of MM cells in vitro. We also preliminarily confirmed that secreting exosomes by ceramide pathway could modulate the proliferation, invasion and tube formation of vascular cells. However, the specific mechanism is unknown. In this project, we speculate that exosomes secreted via the modification of ceramide pathway could influence the angiogenesis of myeloma. We intend to carry out the experiments as follows: 1) investigate the functions of vascular cells by targeting the ceramide pathway; 2) testify the exosomal miRNAs could regulate the angiogenesis of MM via ceramide pathway; 3) figure out the specific mechanisms of exosomal miRNAs in the role of MM angiogenesis. Our study could provide a novel sight into the MM treatment and the anti-angiogenesis treatment.

多发性骨髓瘤（MM）外泌体通过调控血管新生为MM细胞生长及侵袭创造有利条件。神经酰胺（Ceramide）通路是细胞外泌体及外泌体中微小RNA（miRNAs）释放的主要机制之一。我们前期研究发现：Ceramide可调控MM细胞外泌体及外泌体中miRNAs的释放。我们预实验初步证实Ceramide通过调控MM外泌体的释放影响内皮细胞增殖、迁移及成管，但具体机制不明。因此，我们提出假设：Ceramide可通过调控外泌体中miRNAs释放介导MM血管新生。为证实这一假设，我们将进行以下研究：1）以正性及负性调控Ceramide通路为切入点，探讨Ceramide调控MM外泌体释放对MM血管新生的影响；2）证实Ceramide通过调控MM外泌体中miRNAs功能参与MM血管新生；3）阐明MM外泌体中miRNAs通过Akt信号通路介导MM血管新生的具体分子机制，为治疗MM及其血管新生提供新的思路。

多发性骨髓瘤（MM）外泌体通过调控血管新生为MM细胞生长及侵袭创造有利条件。神经酰胺（Ceramide）通路是细胞外泌体及外泌体中微小RNA（miRNAs）释放的主要机制之一。我们前期研究发现：Ceramide可调控MM细胞外泌体及外泌体中miRNAs的释放。我们预实验初步证实Ceramide通过调控MM外泌体的释放影响内皮细胞增殖、迁移及成管，但具体机制不明。因此，我们提出假设：Ceramide可通过调控外泌体中miRNAs释放介导MM血管新生。为证实这一假设，我们将进行以下研究：1）以正性及负性调控Ceramide通路为切入点，探讨Ceramide调控MM外泌体释放对MM血管新生的影响；2）证实Ceramide通过调控MM外泌体中miRNAs功能参与MM血管新生；3）阐明MM外泌体中miRNAs通过Akt信号通路介导MM血管新生的具体分子机制，为治疗MM及其血管新生提供新的思路。