Lin Hua1, Lifa Huang1,2, Xin Zhang2, Haoke Feng1, Bin Shen1. 1. First Clinical Medical College, Zhejiang Chinese Medical University. 2. Department of Neurosurgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Abstract
BACKGROUND: Circular RNAs serve as key players in the development of tumorigenesis and chemoresistance. Circular RNA CEP128 has been reported to be involved in the development of chemoresistance. However, the role of circular RNA CEP128 in the resistance of glioma cells to temozolomide has not yet been characterized. METHODS: The expression of circular RNA CEP128, miR-145-5p, and ATP-binding cassette super-family G member 2 was evaluated using quantitative real-time PCR and western blot. The effects of circular RNA CEP128 on glioma cell proliferation and chemoresistance were evaluated by cell count kit-8 assay and colony formation assay. Luciferase reporter assay was performed for target validation. RESULTS: Circular RNA CEP128 was upregulated in glioma tissues and cell lines. Moreover, circular RNA CEP128 expression was higher in temozolomide-resistant glioma cells compared with that in their parental cells. Knockdown of circular RNA CEP128 inhibited cell proliferation, reduced the expression of ATP-binding cassette super-family G member 2, as well as reduced resistance to temozolomide in glioma cells. Additionally, miR-145-5p was underexpressed in glioma cells as well as temozolomide-resistant glioma cells. Also, miR-145-5p was identified as a target of circular RNA CEP128. Overexpression of miR-145-5p inhibited the proliferation of U251/temozolomide cells and reduced the expression of ATP-binding cassette super-family G member 2, however, these changes induced by miR-145-5p overexpression were blocked by circular RNA CEP128 overexpression. CONCLUSION: Knockdown of circular RNA CEP128 suppresses cell proliferation and improves the cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p, suggesting that circular RNA CEP128 might be a promising target for overcoming the resistance of glioma cells to temozolomide.
BACKGROUND: Circular RNAs serve as key players in the development of tumorigenesis and chemoresistance. Circular RNA CEP128 has been reported to be involved in the development of chemoresistance. However, the role of circular RNA CEP128 in the resistance of glioma cells to temozolomide has not yet been characterized. METHODS: The expression of circular RNA CEP128, miR-145-5p, and ATP-binding cassette super-family G member 2 was evaluated using quantitative real-time PCR and western blot. The effects of circular RNA CEP128 on glioma cell proliferation and chemoresistance were evaluated by cell count kit-8 assay and colony formation assay. Luciferase reporter assay was performed for target validation. RESULTS: Circular RNA CEP128 was upregulated in glioma tissues and cell lines. Moreover, circular RNA CEP128 expression was higher in temozolomide-resistant glioma cells compared with that in their parental cells. Knockdown of circular RNA CEP128 inhibited cell proliferation, reduced the expression of ATP-binding cassette super-family G member 2, as well as reduced resistance to temozolomide in glioma cells. Additionally, miR-145-5p was underexpressed in glioma cells as well as temozolomide-resistant glioma cells. Also, miR-145-5p was identified as a target of circular RNA CEP128. Overexpression of miR-145-5p inhibited the proliferation of U251/temozolomide cells and reduced the expression of ATP-binding cassette super-family G member 2, however, these changes induced by miR-145-5p overexpression were blocked by circular RNA CEP128 overexpression. CONCLUSION: Knockdown of circular RNA CEP128 suppresses cell proliferation and improves the cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p, suggesting that circular RNA CEP128 might be a promising target for overcoming the resistance of glioma cells to temozolomide.