Research Paper Volume 15, Issue 10 pp 4391—4410
Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1
- 1 School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
- 2 Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
- 3 Guangzhou Southern Medical Laboratory Animal Sci and Tech Co. Ltd., Guangzhou 510515, China
- 4 School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China
- 5 School of Basic Medical Sciences, Guangxi Medical University, Nanning 530000, China
- 6 The Third People’s Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China
- 7 Department of Pathology, School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China
- 8 Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China
- 9 Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 10 Central People’s Hospital of Zhanjiang, Zhanjiang 524000, China
- 11 National Demonstration Center for Experimental Education of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
- 12 Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, China
- 13 Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Received: November 24, 2022 Accepted: May 9, 2023 Published: May 22, 2023
https://doi.org/10.18632/aging.204742How to Cite
Copyright: © 2023 Lei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
Bmi-1: B-cell-specific Moloney murine leukemia virus integration site 1; ChIP: chromatin immunoprecipitation; DNKC: differentiated nonkeratinizing carcinoma; EMT: epithelial-mesenchymal transition; HRY: Hairy gene homolog; NPC: nasopharyngeal carcinoma; N: lymph node metastasis; M: distant metastasis; PTEN: phosphatase and tensin homolog; qRT-PCR: quantitative real-time polymerase chain reaction; RNAi: RNA interference; RPMI 1640: Roswell Park Memorial Institute 1640; shRNA: short hairpin RNA; SP: side population; T: tumor size; UDC: undifferentiated carcinoma.