Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the p53-mediated DNA damage and the intracellular localization of the oncogenic YBX1 protein. However, to translate this finding into the clinic as a gene therapy, it is important to develop effective carriers able to deliver exogenous lncRNAs to the targeted cancer cells. Here, we propose the use of biocompatible sphingomyelin nanosystems comprising DOTAP (DSNs) to carry and deliver a plasmid vector encoding for TP53TG1 (pc(TP53TG1)-DSNs) to a colorectal cancer cell line (HCT-116). DSNs presented a high association capacity and convenient physicochemical properties. In addition, pc(TP53TG1)-DSNs showed anti-tumor activities in vitro, specifically a decrease in the proliferation rate, a diminished colony-forming capacity, and hampered migration and invasiveness of the treated cancer cells. Consequently, the proposed strategy displays a high potential as a therapeutic approach for colorectal cancer.

中文翻译：

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通过 lncRNA TP5​​3TG1-脂质纳米系统调节结直肠肿瘤行为

长链非编码 RNA (lncRNA) 是一类新兴的 RNA，在癌症发病机制中起关键作用。在胃肠道癌症中，TP53 靶标 1 (TP53TG1) 是一种表观遗传调控的 lncRNA，由于其肿瘤抑制特性调节 p53 介导的 DNA 损伤和致癌 YBX1 蛋白的细胞内定位，因此它代表了一个有希望的治疗靶点。然而，要将这一发现作为基因治疗转化为临床，重要的是开发能够将外源性 lncRNA 递送至靶向癌细胞的有效载体。在这里，我们建议使用包含 DOTAP (DSN) 的生物相容性鞘磷脂纳米系统将编码 TP53TG1 (pc(TP53TG1)-DSNs) 的质粒载体携带和递送至结肠直肠癌细胞系 (HCT-116)。DSNs 具有很高的缔合能力和方便的物理化学性质。此外，pc(TP53TG1)-DSNs 在体外显示出抗肿瘤活性，特别是增殖率降低、集落形成能力减弱以及阻碍被处理癌细胞的迁移和侵袭。因此，所提出的策略显示出作为结直肠癌治疗方法的巨大潜力。