细胞周期蛋白D1（cyclin D1）的高度不稳定性是细胞周期G1-S期转变检查点的重要限速步骤，对其调控因素进行解析有助于发现新的靶点遏制肿瘤增殖失控。TCGA数据显示，CCND1在多数胃癌细胞中异常高表达，因此是较好的研究模型。课题组经体内外实验筛选到胃癌细胞中具有显著促增殖作用的功能性lncRNA XLOC_004924，可促进胃癌细胞周期从G1期到S期转变。XLOC_004924不影响cyclin D1蛋白合成但可显著增强后者蛋白稳定性和半衰期。因此我们提出XLOC_004924通过增强cyclin D1稳定性促进肿瘤细胞周期进程的假说。本项目拟从依赖和不依赖cyclin D1磷酸化的泛素蛋白酶体降解途径两个方面，解析其中的关键调控分子和通路蛋白，探讨XLOC_004924促进胃肿瘤细胞增殖的机制；并在细胞和动物水平评估沉默XLOC_004924对胃癌增殖的干预效果。

The high instability of cyclin D1 is an important speed limiting step for the G1-S phase transition checkpoint in the cell cycle, and the analysis of its regulatory factors is helpful to the discovery of new targets to inhibit the uncontrolled proliferation of tumors. TCGA data showed that CCND1 was abnormally highly expressed in most gastric cancer cells, so gastric cancer was a good research model. The functional lncRNA XLOC_004924, which has a significant proliferation-promoting effect in gastric cancer cells, was screened by the research group through in vitro and in vivo experiments. LncRNA XLOC_004924 could promote the transformation of gastric cancer cell cycle from G1 phase to S phase. XLOC_004924 did not affect cyclin D1 protein synthesis but significantly enhanced the stability of the latter protein. Therefore, the hypothesis that XLOC_004924 promotes tumor cell cycle progression by enhancing cyclin D1 stability was proposed. This project intends to analyze the key regulatory molecules and pathway proteins in the ubiquitin-proteasome degradation pathway that is dependent on and independent of cyclin D1 phosphorylation, and to explore the mechanism of XLOC_004924 promoting the proliferation of gastric tumor cells. The effect of silencing XLOC_004924 on gastric cancer proliferation was evaluated at boththe cell and animal levels.