Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1.

Abstract

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is overexpressed in various cancer types. We found that Bmi-1 mRNA levels were elevated in nasopharyngeal carcinoma (NPC) cell lines. In immunohistochemical analyses, high Bmi-1 levels were observed in not only 5 of 38 non-cancerous nasopharyngeal squamous epithelial biopsies, but also in 66 of 98 NPC specimens (67.3%). High Bmi-1 levels were detected more frequently in T3-T4, N2-N3 and stage III-IV NPC biopsies than in T1-T2, N0-N1 and stage I-II NPC samples, indicating that Bmi-1 is upregulated in advanced NPC. In 5-8F and SUNE1 NPC cells, stable depletion of Bmi-1 using lentiviral RNA interference greatly suppressed cell proliferation, induced G1-phase cell cycle arrest, reduced cell stemness and suppressed cell migration and invasion. Likewise, knocking down Bmi-1 inhibited NPC cell growth in nude mice. Both chromatin immunoprecipitation and Western blotting assays demonstrated that Hairy gene homolog (HRY) upregulated Bmi-1 by binding to its promoter, thereby increasing the stemness of NPC cells. Immunohistochemistry and quantitative real-time PCR analyses revealed that HRY expression correlated positively with Bmi-1 expression in a cohort of NPC biopsies. These findings suggested that HRY promotes NPC cell stemness by upregulating Bmi-1, and that silencing Bmi-1 can suppress NPC progression.

• Authors: Ye Lei, Hong-Fen Shen, Qi-Wen Li, Sheng Yang, Hong-Ting Xie, Xu-Feng Li, Mei-Ling Chen, Jia-Wei Xia, Sheng-Chun Wang, Guan-Qi Dai, Ying Zhou, Ying-Chun Li, Shi-Hao Huang, Dan-Hua He, Zhi-Hao Zhou, Jin-Ge Cong, Xiao-Lin Lin, Tao-Yan Lin, Ai-Bing Wu, Dong Xiao, Sheng-Jun Xiao, Xin-Ke Zhang, Jun-Shuang Jia
• Journal: Aging (Aging (Albany NY)) Vol. 15 Issue 10 Pg. 4391-4410 (05 22 2023) ISSN: 1945-4589 [Electronic] United States
• PMID: 37219449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Mice
• Nasopharyngeal Carcinoma (genetics)
• Nasopharyngeal Neoplasms (pathology)
• Mice, Nude
• Cell Line, Tumor
• Nasopharynx (pathology)
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Cell Movement (genetics)