Abstract
Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is an essential regulator in many cellular processes, including differentiation, proliferation, inflammation, pluripotency, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has been reported as a tumor suppressor or an oncogene in many cancers. However, the role of KLF4 in osteosarcoma is largely unknown. Here we found the expression of KLF4 was significantly increased in human osteosarcoma tissues compared with the normal tissues. Elevated KLF4 promoted human osteosarcoma cell proliferation and metastasis. Subsequently, mechanistic studies revealed KLF4 specifically bound the promoter of CRYAB and upregulated CRYAB expression in human osteosarcoma cells. Moreover, we found that KLF4 enhanced osteosarcoma cell proliferation and migration via upregulating CRYAB. Therefore, our studies suggested KLF4 may be a potential target for human osteosarcoma therapy.
Highlights
Osteosarcoma (OS) is the most common type of malignant bone cancer that usually occurs in children and young adults [18, 19]
We identified that the expression of Krüppel-like factor 4 (KLF4) was markedly increased in osteosarcoma tissues compared with the normal bone tissues
The high levels of KLF4 were involved in human osteosarcoma cell proliferation, tumorigenesis, and migration
Summary
Osteosarcoma (OS) is the most common type of malignant bone cancer that usually occurs in children and young adults [18, 19]. Remarkable advances in the combined used of chemotherapy, radiotherapy and surgical ablation of the primary tumor, the 5-year survival rate of osteosarcoma patients is still not more than 30% due to its metastasis and recurrence [11]. It is very important to uncover the molecular mechanisms by which OS initiates, proliferation, metastasis, and recurrence to develop effective therapeutic strategies for treatment of this disease. Krüppel-like factor 4 (KLF4), known as gutenriched Krüppel-like factor, is a zinc-finger transcription factor which regulates various biological processes, including cell cycle progression, differentiation, proliferation, inflammation, apoptosis and stem cell renewal [1, 2, 9, 12, 21, 29].
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