Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1

被引:11
作者
Xu, Tongxin [1 ]
Yan, Zhaoyang [2 ]
Lu, Juntao [3 ]
Chen, Liying [3 ]
Li, Xiaoxu [3 ]
Li, Yan [3 ]
Dong, Zhiming [3 ]
Guo, Wei [3 ]
机构
[1] Hebei Med Univ, Dept CT & MRI, Hosp 4, Shijiazhuang, Hebei, Peoples R China
[2] Hebei Med Univ, Dept Thorac Surg, Hosp 4, Shijiazhuang, Hebei, Peoples R China
[3] Hebei Med Univ, Hebei Canc Inst, Lab Pathol, Hosp 4, Jiankang Rd 12, Shijiazhuang 050011, Hebei, Peoples R China
基金
中国国家自然科学基金;
关键词
Esophageal squamous cell carcinoma; lncRNA NRSN2-AS1; SOX2; PGK1; Ubiquitination; CANCER PROGRESSION; PROLIFERATION; LNCRNA; EXPRESSION; ESCC; SLUG;
D O I
10.1007/s10585-022-10174-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aberrant expression of long non-coding RNAs (lncRNAs) plays pivotal roles in tumorigenesis of human malignant cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific role of lncRNA NRSN2-AS1 in ESCC has not been investigated. Our analysis of clinical data revealed that NRSN2-AS1 was upregulated in ESCC tissues and negatively correlated with patient survival. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that NRSN2-AS1 is transcribed by SOX2. In vitro functional experiments showed that NRSN2-AS1 can promote ESCC cell proliferation, migration, and invasion. Furthermore, NRSN2-AS1-binding proteins were detected using RNA pull-down assays and mass spectrometry. Mechanistically, NRSN2-AS1 can bind to phosphoglycerate kinase 1 (PGK1) and upregulate its protein levels by inhibiting its ubiquitination. Knockdown of PGK1 in part abolished the NRSN2-AS1 overexpression-induced effects on ESCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Thus, NRSN2-AS1 may be a diagnostic biomarker or treatment target for ESCC.
引用
收藏
页码:757 / 769
页数:13
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