Lee Young-Sun, Kwon Osung, Jeong Geuk-Rae, Noh Junyeol, Kim Sung Eun, Yi Gwan-Su, Hwang Eun Mi, Park Jae-Yong
School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Korea.
Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
Life (Basel). 2022 Apr 3;12(4):530. doi: 10.3390/life12040530.
The Tweety homolog (TTYH) chloride channel family is involved in oncogenic processes including cell proliferation, invasion, and colonization of cancers. Among the TTYH family, TTYH1 is highly expressed in several cancer cells, such as glioma, breast, and gastric cancer cells. However, the role of TTYH1 in the progression of osteosarcoma remains unknown. Here, we report that deficient TTYH1 expression results in the inhibition of the migration and invasion of U2OS human osteosarcoma cells. We found that TTYH1 was endogenously expressed at both mRNA and protein levels in U2OS cells and that these channels were located at the plasma membrane of the cells. Moreover, we found that silencing of the TTYH1 with small interfering RNA (siRNA) resulted in a decrease in the migration and invasion of U2OS cells, while the proliferation of the cells was not affected. Additionally, treatment with TTYH1 siRNA significantly suppressed the mRNA expression of epithelial−mesenchymal transition (EMT)-regulated transcription factors such as Zinc E-Box Binding Homeobox 1 (ZEB1) and SNAIL. Most importantly, the expression of matrix metalloproteinase (MMP)-2, MPP-9, and N-cadherin was dramatically reduced following the silencing of TTYH1. Taken together, our findings suggest that silencing of TTYH1 expression reduces migration and invasion of U2OS cells and that TTYH1 may act as a potential molecular target for osteosarcoma treatment.
Tweety同源物（TTYH）氯化物通道家族参与致癌过程，包括癌症的细胞增殖、侵袭和定植。在TTYH家族中，TTYH1在几种癌细胞中高表达，如神经胶质瘤、乳腺癌和胃癌细胞。然而，TTYH1在骨肉瘤进展中的作用尚不清楚。在此，我们报告TTYH1表达缺陷导致U2OS人骨肉瘤细胞迁移和侵袭受到抑制。我们发现TTYH1在U2OS细胞的mRNA和蛋白质水平均有内源性表达，且这些通道位于细胞的质膜上。此外，我们发现用小干扰RNA（siRNA）沉默TTYH1会导致U2OS细胞的迁移和侵袭减少，而细胞增殖不受影响。另外，用TTYH1 siRNA处理显著抑制了上皮-间质转化（EMT）调控转录因子如锌指E盒结合同源框1（ZEB1）和SNAIL的mRNA表达。最重要的是，沉默TTYH1后，基质金属蛋白酶（MMP）-2、MPP-9和N-钙黏蛋白的表达显著降低。综上所述，我们的研究结果表明，沉默TTYH1表达可降低U2OS细胞的迁移和侵袭，并且TTYH1可能作为骨肉瘤治疗的潜在分子靶点。
