EBV编码miR-BART22靶向LMP2A改善鼻咽癌干细胞放射抵抗

鼻咽癌干细胞(NPC CSCs)是NPC放射抵抗根本原因之一，EBV编码miR-BART22可靶向抑制LMP2A表达，后者诱导NPC CSCs形成导致放射抵抗。近期我们构建miR-BART22不同水平C666-1细胞，发现高表达miR-BART22可改善放射抵抗。因此我们推测mi-BART22可能通过调控LMP2A抑制NPC CSCs生成，提高NPC放射敏感性。为验证这一假说，我们拟分离培养NPC CSCs，构建miR-BART22不同水平NPC细胞株与NPC CSCs，观察其生物学行为、干性、体内外放射敏感性以及相关信号通路的变化。并针进一步上下调节LMP2A在NPC细胞株与NPC CSCs中表达，观察是否逆转miR-BART22各种生物学效应，以期明确miR-BART2在NPC CSC放射抵抗中的作用及机制。本项目有望进一步阐释NPC放射抵抗机制，为NPC提供新的治疗靶点。

Nasopharygeal carcinoma cancer stem cells (NPC CSCs) is one of the key reasons for radiation resistance. Epstein-Barr virus-encoded microRNA miR-BART22 can inhibit LMP2A expression, which can induce radiation resistance mediated by NPC CSCs. Presently, through construction of high miR-BART22 expression cells C666-1, we found that high-level expression of miR-BART22 can increase radiosensitivity. Therefore, we assume that miR-BART22 may inhance radiosensitivity by decreasing production of NPC CSCs via inhiting LMP2A expression. In order to testify the above theories, we plan to measure miR-BART22 levels in clinical blood samples for correlation analysis. Meanwhile, we plan to isolate and culture NPC CSCs, construct miR-BART22 infected NPC CSCs, and observe its biological behaviour, characteristics of stem cells, radiosensitivity as well as tumor size changes. Thereafter, we aim to culture NPC CSCs infetcted with different levels of LMP2A so as to investigate whether it can reverse the biological effect of miR-BART22 and the down-stream signal molecular cells, in order to reveal the effect and mechanism of miR-BART22 in NPC CSCs radiation resistance.