为探究核仁蛋白（ribosomal L1-domain-containing protein 1,RSL1D1）对印迹基因（paternally expressed 10,PEG10）及下游通路的调控机制,以HepG2肝细胞癌细胞和HCT116结直肠癌细胞为研究对象,通过转录组测序、蛋白质免疫印迹、实时荧光定量PCR、cell counting kit-8法、碘化丙啶染色等方法,考察了RSL1D1、PEG10敲低或过表达后,RSL1D1、PEG10、MYC原癌基因（MYC proto-oncogene,c-Myc）、细胞周期调节基因Cyclin B1表达水平的变化,及其对细胞周期和细胞增殖的影响。结果表明:RSL1D1通过上调c-Myc激活靶基因PEG10转录。在HepG2细胞（RSL1D1和PEG10高表达）中,PEG10敲低通过下调Cyclin B1诱导G2/M阻滞,而在RSL1D1和PEG10低表达的HCT116细胞,敲低PEG10难以影响Cyclin B1介导的细胞增殖。综上,PEG10作为本研究新发现的RSL1D1下游靶分子,在RSL1D1-c-Myc-...

C-MYC is a proto-oncoprotein whose dysregulation triggers tumorigenesis and tumor progression in 70% of cancer cases. It is presently demonstrated that aberrantly upregulated MYC is caused by the overexpressed and "extra-nucleolar" PDCD11 in p53-mutant breast and colon cancer cells, which is highly correlated to tumor progression, metastasis, and recurrence. In the nucleoplasm, PDCD11 binds to the TAD of C-MYC to prevent SKP2, a transcriptional target of C-MYC as well as one of the major E3 ligase components targeting C-MYC, from interacting with and ubiquitinating C-MYC in feedback. The ensuing stabilized C-MYC activates downstream signaling to facilitate the cellular G1/S transition, proliferation, and migration. PDCD11 silencing restores SKP2-mediated C-MYC degradation, thereby remarkably suppressing tumor growth and metastasis in nude mice. These findings highlight PDCD11 as a novel C-MYC partner and thereby offer a potential therapeutic rationale to challenge PDCD11-mediated "pro-stabilization" effect on C-MYC, a widely considered "undruggable" target, to combat C-MYC-driven malignancies with p53 mutation. © 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell-mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor-homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor-targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4-granzyme B-dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter-supplementary biohybrid system.

肿瘤免疫疗法作为一种高效高安全性的抗肿瘤策略,主要通过激活人体免疫系统发挥抗肿瘤效应。多种纳米材料在肿瘤免疫治疗研究中被用于免疫佐剂和疫苗的肿瘤靶向递送。该文主要综述了纳米金作为免疫药物和药物载体在抗肿瘤研究中的应用。纳米金不仅能通过自身的独特优势发挥免疫调节作用,还能够特异性地在体内将免疫制剂运送至效应部位,降低药物的不良反应,提升了免疫药物的作用效果,保障了免疫疗法的安全实施,为肿瘤治疗提供了新思路和新策略。

细胞衰老抑制基因(Rsl1d1,CSIG)是一种核仁蛋白，主要定位于核仁，具有促进细胞增殖的功能，与肿瘤的发生发展密切相关。据报道,RSL1D1在核仁应激条件下释放至核浆，能够与HDM2相互作用，通过抑制p53负调控者HDM2的活性提升肺癌细胞和骨肉瘤细胞中p53蛋白水平。但我们依托该项目的研究表明,RSL1D1在结直肠细胞中对p53-HDM2信号通路的调节与之前的报道恰恰相反，其亚细胞定位不仅仅局限于核仁中，而是在正常条件下就散布于整个细胞核中。RSL1D1在HCT116结直肠癌细胞中，不仅能够通过提升HDM2的mRNA稳定性上调后者蛋白水平，还能够直接与p53和HDM2相互作用，通过形成三联复合体促进HDM2对p53的泛素化降解作用。体内外研究数据表明,RSL1D1敲低能够通过激活p53信号通路，抑制结直肠癌细胞在体内外的生长，揭示了RSL1D1是一种潜在的结直肠癌治疗靶点，利用不同手段抑制RSL1D1-p53、RSL1D1-HDM2相互作用是一种极具潜力的结直肠肿瘤治疗方案。

肿瘤抑制基因p53的突变是细胞癌变中最为常见的基因变化。突变后的p53不仅失去对肿瘤发生的监控作用,而且会获得"致癌性功能增强效应",激活相关促癌信号通路,加速推动肿瘤的进展过程。p53在肿瘤中的高频率突变推动了一系列研究工作的实施,以开发针对p53突变的肿瘤靶向策略。近期研究证实,多种小分子化合物和多肽类药物能通过诱变p53突变体的空间构象和折叠方式以恢复其野生型活性,或通过促进p53突变蛋白的降解抑制其致癌活性,最终抑制肿瘤生长。鉴于目前多种该类药物接近或已进入临床实验阶段,综述靶向突变型p53的抗癌药物的研究进展,以揭示针对p53突变的肿瘤靶向策略良好的临床应用前景。