辅助放疗对瘢痕疙瘩（KL）具有较好疗效，但仍有部分难治性KL对治疗抵抗；长链非编码（lnc）RNA在KL放疗抵抗中的作用尚不清楚。我们通过预实验发现，lncRNA RNF144A-AS1在放疗抵抗KL组织及细胞中表达水平升高，并参与糖酵解途径，与KL放疗抵抗密切相关；进一步研究发现，其可能与缺氧诱导因子-1α（HIF-1α）蛋白结合，抑制泛素化降解而增加蛋白稳定性；而HIF-1α可能结合RNF144A-AS1启动子并激活其表达。由此我们推测RNF144A-AS1与HIF-1α形成正反馈环路，参与糖酵解，导致KL放疗抵抗。本项目拟采用RIP、RNA pull down、荧光素酶报告实验、EMSA等技术，从临床组织、细胞、分子、动物模型等层面，深入探讨RNF144A-AS1在KL放疗抵抗中糖酵解的作用，阐明RNF144A-AS1与HIF-1α相互调控的分子机制，为寻找潜在的治疗靶点提供新思路。

Adjuvant radiotherapy is one of the most effective treatment for keloids (KL) postoperatively. However, recurrence of KL still occurs in some refractory cases and the underlying role of long non-coding RNA remains unclear in it. Our previous data showed that the long non-coding RNA RNF144A-AS1, which may be involved in the glycolytic pathway, was significantly up-regulated in KL tissues and cells which were resistant to radiotherapy. We also found that RNF144A-AS1 may bind to hypoxia inducible factor-1α (HIF-1α) and increase the stabilization of HIF-1α by inhibiting VHL-mediated ubiquitination and degradation, while HIF-1α may bind to the RNF144A-AS1 promoter to activate its expression. Therefore, we hypothesis that there may be a positive feedback loop between RNF144A-AS1 and HIF-1α, which promotes HIF-1α-mediated glycolysis and contributes to the radioresistance in KL. In this project, by using RIP-PCR, RNA pull down, luciferase reporter gene assay, EMSA and other molecular biological technologies, we aims to investigate how RNF144A-AS1 functions in the glycolytic pathway and in KL radioresistance, and the underlying molecular mechanism of positive reciprocal regulation between RNF144A-AS1 and HIF-1α in clinical samples, cells, and mouse models. In conclusion, our objective is to provide new insights into the radioresistance of KL, which may be useful in the future targeted therapy and prognosis evaluation.