【佳学基因检测】LRSAM1 E3 泛素连接酶通过 p53/p21 信号传导障碍促进绒癌进展和转移

小孩基因突变发育迟缓评价

探索肿瘤的基因组学特征与治疗方案设计体会到《Biomed Res Int》在. 2022 Aug 31;2022:1926605.发表了一篇题目为《LRSAM1 E3 泛素连接酶通过 p53/p21 信号传导障碍促进绒癌进展和转移》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Qiumin Li, Ying Wang, Feifei Liu, Haili Wang, Yangyang Fan 等完成。促进了肿瘤的正确治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及正确治疗临床研究内容关键词：

肿瘤靶向治疗基因检测临床应用结果

目的：E3 泛素连接酶 LRSAM1 (LRSAM1) 与许多癌症有关，但它是否对绒癌细胞结构发挥抗癌或促癌作用仍不清楚。我们想探索LRSAM1异常表达对人绒癌细胞结构的影响及其潜在机制。方法：LRSAM1 mRNA在绒癌细胞JEG-3和JAR细胞结构以及HTR8/sev8人滋养层细胞系细胞结构中的表达，使用定量实时聚合酶链反应的测定分析进行评估。我们使用 CCK-8、克隆形成、Transwell、粘附和流式细胞术测定比较了用 si-LRSAM1 质粒感染的细胞结构与阴性对照之间的细胞增殖、迁移流、侵袭力、粘附和凋亡过程。 LRSAM1、E-钙粘蛋白和 N-钙粘蛋白（上皮-间质转化的指标）和 p53/p21 通路成分的蛋白质表达使用蛋白质印迹法进行定量。使用免疫组织化学 (IHC) 分析在异种移植裸鼠中观察肿瘤病变的形态。结果：与 HTR8/sev8 滋养层细胞结构相比，LRSAM1 在 JEG-3 和 JAR 绒癌细胞结构中明显过表达。与 si-NC 相比，LRSAM1 敲低有力地限制了细胞增殖、迁移流动、侵袭力和粘附，并促进了 JEG-3 和 JAR 细胞结构中的凋亡细胞过程并抑制了肿瘤生长，如肿瘤体积的减少和接种转染细胞结构的裸鼠体重。与 si 阴性对照 (si-NC) 相比，si-LRSAM1 显着降低了 Ki67（增殖指标）和 N-cadherin 表达，但降低了 JEG-3 和 JAR 细胞结构中的 E-cadherin 表达。 pifithrin-a（一种p53限制因子）阻断p53/p21通路成功逆转了LRSAM1缺失的抗抑制作用，导致JEG-3和JAR细胞结构的增殖和转移增强。结论：LRSAM1在绒毛膜癌中发挥致瘤作用。通过激活 p53/p21 信号通路和阻碍绒癌细胞增殖、迁移流动和侵袭力，LRSAM1 敲低减缓了疾病的进程。对于绒毛膜癌的诊断和治疗，它是一种新的治疗靶点。

肿瘤发生与反复转移国际数据库描述：

Objective: The E3 ubiquitin ligase LRSAM1 (LRSAM1) was involved in many cancers, but whether it exerts anti- or protumor efficacies on choriocarcinoma cellular structures remains unknown. We wanted to explore the efficacies of aberrant LRSAM1 expression on human choriocarcinoma cellular structures and the underlying mechanisms.Methods: LRSAM1 mRNA expressions in choriocarcinoma lines of cells JEG-3 and JAR cellular structures, as well as HTR8/sev8 human trophoblastic cell line cellular structures, were assessed using assay analysis of quantitative real-time polymerase chain reactions. We compared cell proliferation, migratory flow, invasive force, adhesion, and apoptotic process between cellular structures infected with si-LRSAM1 plasmids versus negative controls using CCK-8, clone formation, Transwell, adhesion, and flow cytometry assays. Protein expressions of LRSAM1, E-cadherin, and N-cadherin (indicators of epithelial-mesenchymal transformation) and p53/p21 pathway components were quantitated using a Western blot assay. The morphology of tumor lesions was observed in xenografted nude mice using immunohistochemistry (IHC) analyses.Results: LRSAM1 was markedly overexpressed within JEG-3 and JAR choriocarcinoma cellular structures compared to HTR8/sev8 trophoblast cellular structures. Compared to si-NC, LRSAM1 knockdown robustly restricted cell proliferating, migratory flow, invasive force, and adhesion and fueled apoptotic cell process in JEG-3 as well as JAR cellular structures and suppressed tumor growth, as evidenced by the reduction in tumor volume and weight in naked mice inoculated with transfected cellular structures. Compared to si-negative control (si-NC), si-LRSAM1 significantly decreased Ki67 (a proliferating indicator) and N-cadherin expressions but reduced E-cadherin expression in JEG-3 and JAR cellular structures. Blocking the p53/p21 pathway by pifithrin-a (a p53 restrictor) successfully reversed the anti-inhibitory effect of LRSAM1 depletion, resulting in enhanced proliferating and metastasis in JEG-3 and JAR cellular structures.Conclusion: LRSAM1 exerts tumorigenic roles in choriocarcinoma. Via the activating of the p53/p21 pathway of signaling and impediment of choriocarcinoma cell proliferating, migratory flow, and invasive force, LRSAM1 knockdown slows the course of the disease. For choriocarcinoma diagnosis and treatment, it serves as a new therapeutic target.