Mucin 1 (MUC1) is a transmembrane glycoprotein involved in the development and progression of various cancers. However, the role of MUC1 in glioblastoma (GBM) remains unclear. Here, researchers investigated the anti-cancer mechanism of MUC1 inhibition in GBM. MUC1 expression levels were analyzed in human glioma and matched normal brain tissue. Results showed that MUC1 was overexpressed in GBM and negatively correlated with overall survival. Furthermore, MUC1 gene knockdown was performed to investigate its effects in GBM cell lines. Results showed that MUC1 knockdown inhibited cell proliferation and caused cell cycle arrest in the G1 phase. MUC1 knockdown decreased RB1 phosphorylation and increased CDKN1B expression. Gene set enrichment analysis revealed that a series of genes related to cell cycle, telomere maintenance, and transforming growth factor β (TGF-β) signaling during epithelial-mesenchymal transition (EMT) were affected by MUC1 knockdown. Notably, knockdown of MUC1 reduced TERT expression, impaired telomerase activity, and shifted the telomere maintenance mechanism to alternative telomere lengthening (ALT). These findings support the role of MUC1 in glioblastoma (GBM) tumor progression and suggest that MUC1 could be a therapeutic target for cell cycle regulation and telomere maintenance mechanisms.
To investigate the potential mechanism underlying the decreased cell viability caused by MUC1 knockdown, the researchers performed cell cycle analysis. Flow cytometry revealed that after MUC1 knockdown, the cell cycle arrested at the G0/G1 phase (Figures 1A and B). Among G1 phase cell cycle regulators, CDKN1B protein expression was upregulated, while phosphorylation of retinoblastoma 1 (RB1) was decreased after MUC1 knockdown (Figure 1C). Control and MUC1 knockdown cells were stained with Annexin V and 7-AAD to investigate whether G1 phase cell cycle arrest was associated with apoptosis. However, there was no statistically significant difference in apoptosis rates between control and MUC1 knockdown cells.
Figure 1. MUC1 knockdown attenuates cell cycle progression at G1 phase. (Kim S, et al., 2020)