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Published on: March 5, 2019
Upregulated TTYH2 expression is critical for the invasion and migration of U2OS human osteosarcoma cell lines
Dong Kyu Moon1, Yeon Ju Bae2, Geuk-Rae Jeong2
1Department of Orthopedic Surgery and Institute of Health Sciences, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea.
Abstract:
Ion channels have recently emerged as stable biomarkers and anticancer targets particularly when the applications of the currently available therapeutic regimens are limited, as in case of osteosarcoma, a malignant bone tumor. Here, we evaluated the expression of TTYH2, a presumably calcium-activated chloride channel, in a human osteosarcoma cell line U2OS. We used small-interfering RNA (siRNA)-mediated gene silencing to demonstrate the downregulation in the expression of TTYH2 that resulted in the decrease in the invasion and migration, but not proliferation, of U2OS cells. The expression levels of Slug and ZEB1, the transcription factors involved in epithelial-mesenchymal transition, significantly reduced after TTYH2 silencing. Based on these results, we suggest that TTYH2 may serve as a novel target for the treatment of osteosarcoma.
Insights
TTYH2, a calcium-activated chloride channel, is downregulated in osteosarcoma cells, reducing invasion and migration. This suggests TTYH2 is a potential therapeutic target for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ion channels are emerging as promising biomarkers and therapeutic targets in oncology, especially for cancers like osteosarcoma where current treatments have limitations.
- Osteosarcoma, a malignant bone tumor, presents a significant challenge due to limited therapeutic options.
- TTYH2, a calcium-activated chloride channel, has been implicated in cellular processes, but its role in osteosarcoma remains largely unexplored.
Purpose of the Study:
- To investigate the expression and functional role of TTYH2 in human osteosarcoma cells.
- To determine if TTYH2 can be a potential therapeutic target for osteosarcoma.
Main Methods:
- Utilized a human osteosarcoma cell line (U2OS).
- Employed small-interfering RNA (siRNA)-mediated gene silencing to downregulate TTYH2 expression.
- Assessed the impact of TTYH2 silencing on cell invasion, migration, proliferation, and the expression of epithelial-mesenchymal transition (EMT) markers (Slug and ZEB1).
Main Results:
- Downregulation of TTYH2 expression was successfully achieved using siRNA.
- Silencing TTYH2 significantly decreased the invasion and migration capabilities of U2OS cells.
- TTYH2 silencing did not affect the proliferation of U2OS cells.
- Expression levels of EMT-associated transcription factors, Slug and ZEB1, were significantly reduced following TTYH2 silencing.
Conclusions:
- TTYH2 plays a crucial role in regulating osteosarcoma cell invasion and migration, likely through its influence on EMT.
- TTYH2 represents a novel and promising therapeutic target for osteosarcoma treatment.
- Further research into TTYH2-targeting therapies could lead to improved treatment strategies for osteosarcoma.
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