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

作者：Lei, Ye; Shen, Hong-Fen; Li, Qi-Wen; Yang, Sheng; Xie, Hong-Ting; Li, Xu-Feng; Chen, Mei -Ling; Xia, Jia-Wei; Wang, Sheng-Chun; Dai, Guan-Qi; Zhou, Ying; Li, Ying-Chun; Huang, Shi-Hao; He, Dan-Hua; Zhou, Zhi-Hao; Cong, Jin-Ge; Lin, Xiao-Lin; Lin, Tao-Yan; Wu, Ai -Bing; Xiao, Dong^*; Xiao, Sheng-Jun^*; Zhang, Xin-Ke^*; Jia, Jun-Shuang^*

来源：Aging-US, 2023, 15(10): 4391-4410.

• nasopharyngeal carcinoma (NPC)
• Bmi-1
• HRY
• cell proliferation
• migration

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.

• 单位
  广东医学院; 中山大学; xk; 南方医科大学; 6