Inhibition of MUC1 exerts cell-cycle arrest and telomerase suppression in glioblastoma cells

• Published in: Scientific reports Vol. 10; no. 1; p. 18238
• Main Authors: Kim, Sojin, Seo, Youngbeom, Chowdhury, Tamrin, Yu, Hyeon Jong, Lee, Chae Eun, Kim, Kyung-Min, Kang, Ho, Kim, Hak Jae, Park, Soo-Ji, Kim, Kyoungmi, Park, Chul-Kee
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-10-2020; Nature Publishing Group
• Subjects: 631/337; 631/67; 692/308; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell lines; Cell Movement; Cell Proliferation; G1 phase; Gene set enrichment analysis; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioma; Humanities and Social Sciences; Humans; Mesenchyme; Mucin; Mucin-1 - genetics; Mucin-1 - metabolism; multidisciplinary; Phosphorylation; Science; Science (multidisciplinary); Signal Transduction; Survival Rate; Telomerase; Telomerase - antagonists & inhibitors; Telomerase - genetics; Telomerase - metabolism; Telomere Homeostasis - genetics; Telomeres; Transforming growth factor-b; Tumorigenesis; Yeast
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-75457-z

Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of
MUC1
suppression in GBM was investigated. The expression level of
MUC1
was analyzed in human glioma and paired normal brain tissues.
MUC1
was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced
MUC1
to investigate its effect in GBM cell lines and found that knockdown of
MUC1
inhibited cell proliferation and resulted in cell cycle arrest at G1 phase.
MUC1
silencing decreased the phosphorylation of
RB1
and increased the expression of
CDKN1B
. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by
MUC1
knockdown. Notably, the reduced
TERT
expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after
MUC1
knockdown. Our results support the role of
MUC1
in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.