Center for Medical Education and Sciences, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
PLoS One. 2018 Jul 3;13(7):e0199442. doi: 10.1371/journal.pone.0199442. eCollection 2018.
Snail, also called Snai1, is a key regulator of EMT. Snail plays crucial roles in cancer progression, including resistance to anti-tumor drugs and invasion by various cancer cells. Slug, also known as Snai2, is also involved in the aggravation of certain tumors. In this study, we examined the roles of Slug in human oral squamous cell carcinoma (OSCC) cells. Slug is highly expressed in these cells, and Slug siRNA effectively represses anti-tumor drug resistance and invasive properties. In addition, transforming growth factor (TGF)-β upregulates the expression of Snail and Slug and promotes resistance to anti-tumor drugs in OSCC cells. Surprisingly, Slug siRNA appears to upregulate Snail expression considerably in OSCC cells. Snail siRNA also appears to upregulate Slug expression. Thus, either Slug or Snail siRNA alone partially mitigates malignant phenotypes in the presence of TGF-β, whereas both Slug and Snail siRNAs together dramatically suppress them. Therefore, Slug and Snail in tandem, but not alone, are potential therapeutic targets for nucleic acid medicines to treat oral cancer.
蜗牛,也称为 Snai1,是 EMT 的关键调节剂。Snail 在癌症进展中发挥着至关重要的作用,包括对肿瘤药物的耐药性和各种癌细胞的侵袭。Slug,也称为 Snai2,也参与了某些肿瘤的恶化。在这项研究中,我们研究了 Slug 在人口腔鳞状细胞癌(OSCC)细胞中的作用。Slug 在这些细胞中高度表达,Slug siRNA 可有效抑制抗肿瘤药物耐药性和侵袭性。此外,转化生长因子(TGF)-β上调 Snail 和 Slug 的表达,并促进 OSCC 细胞对肿瘤药物的耐药性。令人惊讶的是,Slug siRNA 似乎在 OSCC 细胞中显著上调了 Snail 的表达。Snail siRNA 似乎也上调了 Slug 的表达。因此,在 TGF-β存在的情况下,Slug 或 Snail siRNA 单独使用可部分减轻恶性表型,而 Slug 和 Snail siRNAs 联合使用则可显著抑制它们。因此,Slug 和 Snail 联合而非单独,可能成为治疗口腔癌的核酸药物的潜在治疗靶点。