促进肿瘤显现和发展！中山大学发帖：揭示癌症治疗新靶点
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q7.itc.cn/q_70/images03/20240313/ddc80bea67ef482bb6af2f77229be62a.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">作者：Jerry</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">导读：</strong><span style="color: black;">NSUN2是m5C形成的<span style="color: black;">要紧</span>的RNA甲基转移酶之一，参与许多<span style="color: black;">要紧</span>的生物过程。然而，NSUN2介导的m5C修饰在结直肠癌(CRC)中的<span style="color: black;">功效</span>和潜在的分子机制尚不清楚。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">3月11日，中山大学方乐堃<span style="color: black;">科研</span>团队在期刊《Clinical And Translational Medicine》上<span style="color: black;">发布</span>了<span style="color: black;">科研</span>论文，题为“NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization”。<strong style="color: blue;">本<span style="color: black;">科研</span>强调了NSUN2<span style="color: black;">经过</span>m5c - ybx1依赖的SKIL转录稳定在CRC的初始和<span style="color: black;">发展</span>中的<span style="color: black;">要紧</span>性，为CRC<span style="color: black;">供给</span>了一个有前景的靶向治疗策略。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.1621</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>背景</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">01 </span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">结直肠癌(CRC)是<span style="color: black;">全世界</span>第三大<span style="color: black;">平常</span>癌症。手术是根治性治疗的重头戏。然而，大<span style="color: black;">都数</span>CRC<span style="color: black;">病人</span>因诊断晚和治疗方式<span style="color: black;">没</span>效而死亡。<span style="color: black;">因此呢</span>，迫切<span style="color: black;">必须</span>针对CRC的新型治疗靶点。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">SKIL,<span style="color: black;">亦</span><span style="color: black;">叫作</span>为SnoN，是转化生长因子-β(TGF-β)信号传导的负向<span style="color: black;">掌控</span>器。在哺乳动物中，SnoN在胚胎和成人组织中广泛表达。SKIL在许多癌细胞和组织中表达水平<span style="color: black;">上升</span>，<span style="color: black;">包含</span>来自非小细胞肺癌(NSCLC)和乳腺癌的细胞。有证据<span style="color: black;">显示</span>，SKIL与Hippo通路的多个组分相互<span style="color: black;">功效</span>，<span style="color: black;">控制</span>大肿瘤<span style="color: black;">控制</span>因子激酶2(Lats2)与TAZ的结合，致使TAZ稳定。<span style="color: black;">另外</span>，SKIL<span style="color: black;">经过</span>上调TAZ/自噬轴和<span style="color: black;">控制</span>STING通路促进NSCLC细胞的肿瘤<span style="color: black;">出现</span>和免疫逃逸。相反，<span style="color: black;">有些</span><span style="color: black;">科研</span><span style="color: black;">显示</span>SKIL发挥肿瘤<span style="color: black;">控制</span><span style="color: black;">功效</span>。<span style="color: black;">例如</span>，沉默SKIL<span style="color: black;">增多</span>了食管鳞癌细胞系的增殖，<span style="color: black;">显示</span>了SKIL在肿瘤<span style="color: black;">出现</span>中的<span style="color: black;">繁杂</span><span style="color: black;">功效</span>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span><span style="color: black;">发展</span></strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">02 </span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">为了<span style="color: black;">科研</span>NSUN2对CRC细胞<span style="color: black;">行径</span>的影响，<span style="color: black;">科研</span>人员<span style="color: black;">运用</span>shRNAs敲低NSUN2，并<span style="color: black;">经过</span>蛋白印迹法确定其效率。利用诱导细胞和克隆形成实验来探索NSUN2对CRC细胞增殖的调节<span style="color: black;">功效</span>。<span style="color: black;">另外</span>，重新引入NSUN2挽救了CRC细胞的生长。<span style="color: black;">一样</span>，克隆形成实验<span style="color: black;">显示</span>，NSUN2促进了克隆形成能力。<span style="color: black;">科研</span>人员还<span style="color: black;">发掘</span>，在NSUN2被敲低后，迁移细胞的数量<span style="color: black;">明显</span>减少。相比之下，上调NSUN2<span style="color: black;">增多</span>了细胞的迁移能力。<strong style="color: blue;">挽救实验<span style="color: black;">显示</span>，NSUN2参与了促进CRC细胞迁移的进程，这进一步证实了NSUN2的致癌<span style="color: black;">功效</span>。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">另一</span>，<span style="color: black;">科研</span>人员将稳定感染的DLD1细胞接种到裸鼠的腹侧，观察NSUN2对异种移植瘤生长的影响。与对照组相比，NSUN2敲低组的肿瘤<span style="color: black;">体积</span>和重量<span style="color: black;">显著</span>降低，而重新引入NSUN2后<span style="color: black;">能够</span>挽救。<strong style="color: blue;">总的<span style="color: black;">来讲</span>，这些结果<span style="color: black;">显示</span>，NSUN2在<span style="color: black;">身体</span>外均促进CRC生长。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">科研</span>人员还设计了挽救性功能实验，实验<span style="color: black;">显示</span>，SKIL过表达恢复了NSUN2敲低对CRC细胞增殖、克隆形成和迁移的<span style="color: black;">控制</span><span style="color: black;">功效</span>，相反，SKIL敲低消除了NSUN2促进CRC细胞克隆形成、细胞增殖和迁移的<span style="color: black;">功效</span>。<span style="color: black;">科研</span>人员将shNSUN2和PLVX-SKIL处理过或未处理的DLD1细胞接种到裸鼠的侧腹部。结果<span style="color: black;">表示</span>，NSUN2敲低<span style="color: black;">控制</span>了肿瘤生长，降低了肿瘤重量和Ki67表达水平，而SKIL过表达则挽救了这些效果。<strong style="color: blue;">总之，SKIL是促进CRC恶性肿瘤的<span style="color: black;">重要</span>靶点。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q1.itc.cn/q_70/images03/20240313/d677d623ff2845ee9780a10b654e2ca8.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">NSUN2 - SKIL轴在<span style="color: black;">身体</span>和体外都能促进结直肠癌的<span style="color: black;">发展</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>结论</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">03</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">总之，本<span style="color: black;">科研</span>结果证明了SKIL在CRC中的致癌<span style="color: black;">功效</span>，并将其<span style="color: black;">做为</span>CRC<span style="color: black;">病人</span>预后指标的<span style="color: black;">潜能</span>。本<span style="color: black;">科研</span>结果揭示了<span style="color: black;">经过</span>m5C修饰调节SKIL表达的新机制，这<span style="color: black;">显示</span>SKIL表达的调节机制是表观遗传学介导的，并且<span style="color: black;">控制</span>SKIL中的m5C修饰可能对CRC<span style="color: black;">病人</span>有治疗<span style="color: black;">功效</span>。<strong style="color: blue;">体外和<span style="color: black;">身体</span>实验证明NSUN2<span style="color: black;">经过</span>SKIL促进了CRC的发展。</strong>在CRC肿瘤组织中，NSUN2和SKIL的蛋白表达水平呈<span style="color: black;">明显</span>正<span style="color: black;">关联</span>。<span style="color: black;">因此呢</span>，进一步<span style="color: black;">科研</span>SKIL和NSUN2介导的m5C修饰在CRC中的协同抗癌<span style="color: black;">功效</span>是有<span style="color: black;">道理</span>的。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">参考资料：</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.1621</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">注：本文旨在<span style="color: black;">介绍医学<span style="color: black;">科研</span><span style="color: black;">发展</span>，<span style="color: black;">不可</span><span style="color: black;">做为</span>治疗<span style="color: black;">方法</span>参考。如需<span style="color: black;">得到</span>健康<span style="color: black;">指点</span>，请至正规医院就</span>诊。</p>
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