Glioblastoma (GBM) is a malignant tumor prone to recurrence and resistant to conventional therapies. GBM cells show high autophagy activity, contributing to its rapid progression. Casein kinase 1 family, such as casein kinase 1α (CK1α), has shown its effect on autophagy by binding to the hypoxia-inducible factor-1α (HIF-1α). This study investigates the expression of CK1α and HIF-1α in healthy and GBM tissues and its relations with autophagy-related genes and GBM cell viability. The expressions of CK1α, HIF-1α, and autophagy-related proteins in normal tissues, GBM tissues, and GBM cell lines (U87MG, U251, U118-MG, LN229, and SHG44) were analyzed by qRT-PCR and Western blotting. In vitro, the U87MG cell line was transfected with pcDNA3.1-CK1α to enhance the expression of CK1α or both pcDNA3.1-CK1α and siRNA-HIF-1α. The expression of CK1α, HIF-1α, and autophagy-related proteins in GBM brain tissues and cell lines was higher than in normal brain tissues. In U87MG cells, enhanced CK1α expression upregulated the expression of HIF-1α and autophagy-related proteins and promoted cell proliferation. Inhibiting the expression of HIF-1α reduced the expression of autophagy-related proteins and decreased U87MG cell viability. Overexpressed CK1α positively regulates autophagy activity through the HIF-1α pathway. Inhibition of CK1α might be a potential therapeutic approach for glioblastoma therapy.NEW & NOTEWORTHY The study demonstrated that overexpressed CK1α positively regulated autophagy activity through the HIF-1α pathway to promote the progression. Thus, CK1α might be a potential treatment target for glioblastoma.
Keywords: CK1α; HIF-1α; autophagy; glioblastoma; progression.