机构：[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
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.
基金：
This work was supported by the National Natural Science Foundation of China (grant nos. 82173299, 81872209, 81672689, 81372896 and 81172587 to DX; grant nos. 81870602 and 81600488 to XLL; grant no. 81702778 to JSJ; grant no. 82203251 to TYL; grant nos. 82260476, 82060500, 81760491 and 81560441 to SJX; grant no. 81702953 to SCW), the Natural Science Foundation of Guangdong Province of China (grant nos. 2022A1515012477 and 2014A030313294 to DX; grant no. 2022A1515012467 to JSJ; grant no. 2023A1515011844 to LXL; grant no. 2021A1515111127 to TYL; grant nos. 2023A1515010331 and 2022A1515010018 to ABW), the Science and Technology Planning Project of Guangdong Province of China (grant nos. 2017A010105017, 2013B060300013 and 2009B060300008 to DX; grant no. 2017A030303018 to JSJ; grant no. 2015A030302024 to XLL), the China Postdoctoral Science Foundation (grant nos. 2015M572338, 2016T90792, 2017M622740 and 2018T110884 to X.-L. Lin), the President Foundation of Nanfang Hospital (grant no. 2020C002 to T.Y. Lin), the Medical Scientific Research Foundation of Guangdong Province of China (grant no. A2017420 to JSJ; grant no. B2014238 to HFS), the Basic Research Foundation of Yunnan Province Local Universities (grant no. 202001BA070001-063 to JWX), the Science and Technology Planning Project of Kunming City of China (grant no. 2019-1-S-25318000001329 to JWX), the Scientific Research Start-up Plan of Young Scientific Scholars of Southern Medical University (grant no. B1012108 to HFS) and the Science Research Foundation of Guangdong Medical University (grant no. B2017005 to S.C. Wang).
第一作者机构：[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
共同第一作者：
通讯作者：
通讯机构：[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 [11]National Demonstration Center for Experimental Education of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
推荐引用方式(GB/T 7714)：
Ye Lei,Hong-Fen Shen,Qi-Wen Li,et al.Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1[J].AGING-US.2023,15(10):4391-4410.doi:10.18632/aging.204742.
APA：
Ye Lei,Hong-Fen Shen,Qi-Wen Li,Sheng Yang,Hong-Ting Xie...&Jun-Shuang Jia.(2023).Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1.AGING-US,15,(10)
MLA：
Ye Lei,et al."Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1".AGING-US 15..10(2023):4391-4410
