泛素特异性肽酶22（USP22）对关键基因转录的调控在胃癌发生发展中的作用

Ubiquitin specific peptidase 22 (USP22), which belongs to one of the members of the ubiquitin-specific modification enzyme family (UBPs) and is a subunit of the transcription auxiliary complex SAGA, regulates the gene transcription by hydrolyzing the ubiquitin of histone H2A and H2B. Several studies have indicated the promotion role of USP22 in tumor progression recently, but the underlying mechanisms remain elusive. Our preliminary studies showed: ①The expression of USP22 in the low-grade intraepitllelial neoplasia, the early gastric cancer and the advanced gastric cancer tissues had an ascent tendency. ② The cells with USP22 overexpression showed the enhanced cell proliferation and invasion. Taking into account the important regulatory role of USP22 on cell cycle and apoptosis, here, we aim to: ①analyze the USP22 expression in precancerous lesions and the different stages of gastric cancer, combined with follow-up analysis to establish the prognostic model; ②systematically investigate the target genes and the signaling pathways of USP22 using expression profile microarrays.③investigate the underlying molecular mechanisms of USP22 on gene transcription using mass spectrometry, CHIP and other approaches. Thus, the molecular signaling network diagram of USP22 in tumorigenesis and progression of gastric cancer would be well demonstrated. This study could further provide the potential molecular markers as well as therapeutic targets for early detection and treatment of gastric cancer.

泛素特异性肽酶22 (USP22)属于泛素特异性修饰酶家族(UBPs)成员，其为转录辅助复合体SAGA的亚单位，通过水解组蛋白H2A和H2B上的泛素调控基因转录。近年发现USP22对肿瘤进展有促进作用，但无进一步报道。我们前期研究示：①在低级别上皮内瘤变、早期胃癌、进展期胃癌组织中，USP22的表达呈上升趋势；②USP22过表达细胞增殖和侵袭能力均明显增强。考虑到USP22对细胞周期和凋亡的重要调控作用，本研究拟：①分析USP22在不同进展阶段癌前病变及胃癌中表达，结合随访分析建立预后预测模型；②采用表达谱芯片，系统性地对USP22调控的关键基因转录及信号通路活化进行筛选；③应用质谱分析、CHIP等技术研究USP22调控基因转录的分子机制。从而绘制出USP22调控胃癌发生发展的分子信号网络图，为胃癌的预防、早诊早治提供新的分子标记及潜在治疗靶点。

泛素特异性肽酶22（USP22）属于泛素特异性修饰酶家族（UBPs）成员，其为转录辅助复合体SAGA的亚单位，通过水解组蛋白H2A和H2B上的泛素调控基因转录。近年发现USP22对肿瘤进展有促进作用，但无进一步报道。在项目资助下，研究人员发现：①肿瘤中USP22表达水平随着胃癌进展不断升高，肿瘤内USP22表达水平可作为胃癌患者术后预后的分子标记；②体内外实验阐明了USP22对胃癌发生发展的促进作用；③采用表达谱芯片、免疫共沉淀-质谱分析和染色质免疫共沉淀-片段测序等技术，系统性地鉴定出包含USP22的转录相关蛋白复合体及其直接调控的关键基因转录及信号通路活化。研究初步绘制出USP22调控胃癌发生发展的分子信号网络图，为胃癌早诊早治和预后评估提供了新的分子标记及潜在治疗靶点。