Masoumi Farimah, Saraiva Sofia M, Bouzo Belén L, López-López Rafael, Esteller Manel, Díaz-Lagares Ángel, de la Fuente María
Nano-Oncology and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, 15706 Santiago de Compostela, Spain.
Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran 14176-13151, Iran.
Pharmaceutics. 2021 Sep 18;13(9):1507. doi: 10.3390/pharmaceutics13091507.
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.
长链非编码RNA（lncRNAs）是一类新兴的RNA，在癌症发病机制中起着关键作用。在胃肠道癌症中，TP53靶标1（TP53TG1）是一种受表观遗传调控的lncRNA，因其具有调节p53介导的DNA损伤以及致癌蛋白YBX1的细胞内定位的肿瘤抑制特性，而成为一个有前景的治疗靶点。然而，要将这一发现转化为临床基因治疗方法，开发能够将外源性lncRNAs递送至靶向癌细胞的有效载体至关重要。在此，我们提出使用包含DOTAP的生物相容性鞘磷脂纳米系统（DSNs）来携带并将编码TP53TG1的质粒载体（pc(TP53TG1)-DSNs）递送至结肠癌细胞系（HCT-116）。DSNs具有高结合能力和便利的物理化学性质。此外，pc(TP53TG1)-DSNs在体外显示出抗肿瘤活性，具体表现为处理后的癌细胞增殖率降低、集落形成能力减弱以及迁移和侵袭能力受阻。因此，所提出的策略作为一种结肠癌治疗方法具有很高的潜力。
