2. Academic Validation
  3. SOX1 promotes differentiation of nasopharyngeal carcinoma cells by activating retinoid metabolic pathway

SOX1 promotes differentiation of nasopharyngeal carcinoma cells by activating retinoid metabolic pathway

  • Cell Death Dis. 2020 May 7;11(5):331. doi: 10.1038/s41419-020-2513-1.
Xin-Xing Lei  # 1,  Yun Liu  # 2,  Jin-Xing Wang 3,  Qian Cai 2,  Min Yan 1,  Hui-Ping He 1,  Quentin Liu 4 5,  Zi-Jie Long 6,  Zhong Guan 7
Affiliations

Affiliations

  • 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, 510060, Guangzhou, China.
  • 2 Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, China.
  • 3 Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Institute of Hematology, Sun Yat-sen University, 510630, Guangzhou, China.
  • 4 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, 510060, Guangzhou, China. liuq9@mail.sysu.edu.cn.
  • 5 Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Institute of Hematology, Sun Yat-sen University, 510630, Guangzhou, China. liuq9@mail.sysu.edu.cn.
  • 6 Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Institute of Hematology, Sun Yat-sen University, 510630, Guangzhou, China. longzij@mail.sysu.edu.cn.
  • 7 Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, China. gzhong@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 32382038 DOI: 10.1038/s41419-020-2513-1
Abstract

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

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