【佳學(xué)基因檢測(cè)】LRSAM1 E3 泛素連接酶通過 p53/p21 信號(hào)傳導(dǎo)障礙促進(jìn)絨癌進(jìn)展和轉(zhuǎn)移

小孩基因突變發(fā)育遲緩評(píng)價(jià)

探索腫瘤的基因組學(xué)特征與治療方案設(shè)計(jì)體會(huì)到《Biomed Res Int》在.?2022 Aug 31;2022:1926605.發(fā)表了一篇題目為《LRSAM1 E3 泛素連接酶通過 p53/p21 信號(hào)傳導(dǎo)障礙促進(jìn)絨癌進(jìn)展和轉(zhuǎn)移》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Qiumin Li,?Ying Wang,?Feifei Liu,?Haili Wang,?Yangyang Fan?等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究?jī)?nèi)容關(guān)鍵詞：

腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果

目的：E3 泛素連接酶 LRSAM1 (LRSAM1) 與許多癌癥有關(guān)，但它是否對(duì)絨癌細(xì)胞結(jié)構(gòu)發(fā)揮抗癌或促癌作用仍不清楚。我們想探索LRSAM1異常表達(dá)對(duì)人絨癌細(xì)胞結(jié)構(gòu)的影響及其潛在機(jī)制。方法：LRSAM1 mRNA在絨癌細(xì)胞JEG-3和JAR細(xì)胞結(jié)構(gòu)以及HTR8/sev8人滋養(yǎng)層細(xì)胞系細(xì)胞結(jié)構(gòu)中的表達(dá)，使用定量實(shí)時(shí)聚合酶鏈反應(yīng)的測(cè)定分析進(jìn)行評(píng)估。我們使用 CCK-8、克隆形成、Transwell、粘附和流式細(xì)胞術(shù)測(cè)定比較了用 si-LRSAM1 質(zhì)粒感染的細(xì)胞結(jié)構(gòu)與陰性對(duì)照之間的細(xì)胞增殖、遷移流、侵襲力、粘附和凋亡過程。 LRSAM1、E-鈣粘蛋白和 N-鈣粘蛋白（上皮-間質(zhì)轉(zhuǎn)化的指標(biāo)）和 p53/p21 通路成分的蛋白質(zhì)表達(dá)使用蛋白質(zhì)印跡法進(jìn)行定量。使用免疫組織化學(xué) (IHC) 分析在異種移植裸鼠中觀察腫瘤病變的形態(tài)。結(jié)果：與 HTR8/sev8 滋養(yǎng)層細(xì)胞結(jié)構(gòu)相比，LRSAM1 在 JEG-3 和 JAR 絨癌細(xì)胞結(jié)構(gòu)中明顯過表達(dá)。與 si-NC 相比，LRSAM1 敲低有力地限制了細(xì)胞增殖、遷移流動(dòng)、侵襲力和粘附，并促進(jìn)了 JEG-3 和 JAR 細(xì)胞結(jié)構(gòu)中的凋亡細(xì)胞過程并抑制了腫瘤生長(zhǎng)，如腫瘤體積的減少和接種轉(zhuǎn)染細(xì)胞結(jié)構(gòu)的裸鼠體重。與 si 陰性對(duì)照 (si-NC) 相比，si-LRSAM1 顯著降低了 Ki67（增殖指標(biāo)）和 N-cadherin 表達(dá)，但降低了 JEG-3 和 JAR 細(xì)胞結(jié)構(gòu)中的 E-cadherin 表達(dá)。 pifithrin-a（一種p53限制因子）阻斷p53/p21通路成功逆轉(zhuǎn)了LRSAM1缺失的抗抑制作用，導(dǎo)致JEG-3和JAR細(xì)胞結(jié)構(gòu)的增殖和轉(zhuǎn)移增強(qiáng)。結(jié)論：LRSAM1在絨毛膜癌中發(fā)揮致瘤作用。通過激活 p53/p21 信號(hào)通路和阻礙絨癌細(xì)胞增殖、遷移流動(dòng)和侵襲力，LRSAM1 敲低減緩了疾病的進(jìn)程。對(duì)于絨毛膜癌的診斷和治療，它是一種新的治療靶點(diǎn)。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)際數(shù)據(jù)庫(kù)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.