机构:[1]Hebei Med Univ, Res Ctr, Hosp 4, Shijiazhuang, Hebei, Peoples R China河北医科大学第四医院[2]Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China
Gastric cancer (GC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) have been reported to be the important regulators during the occurrence and development of GC. The present study identified a novel and functional lncRNA in GC, named NR038975, which was confirmed to be markedly upregulated in the Gene Expression Profiling Interactive Analysis (GEPIA) dataset and our independent cohort of GC tissues. We firstly characterized the full-length sequence and subcellular location of NR038975 in GC cells. Our data demonstrated that upregulated NR038975 expression was significantly related to lymph node metastasis and TNM stage. In addition, knockdown of NR038975 inhibited GC cell proliferation, migration, invasion, and clonogenicity and vice versa. Mechanistically, RNA pull-down and mass spectrometry assays identified the NR038975-binding proteins and NF90/NF45 complex, and the binding was also confirmed by RNA immunoprecipitation and confocal experiments. We further demonstrated that genetic deficiency of NR038975 abrogated the interaction between NF45 and NF90. Moreover, NF90 increased the stability of NR038975. Thus, NR038975-NF90/NF45 will be an important combinational target of GC. Finally, we detected NR038975 in serum exosomes and serum of GC patients. Our results indicated that NR038975 was a biomarker for gastric tumorigenesis. The current study demonstrated that NR038975 is a novel lncRNA that is clinically and functionally engaged in GC progression and might be a novel diagnostic marker and potential therapeutic target.
基金:
This work was supported by the Natural Science Foundation of
China (Nos. 81772550, 81673642, 81502032, 81973520, and
81902798), the Outstanding Youth Foundation of Hebei
Province, China (H2019206697), and the Natural Science
Foundation of Hebei Province (H2020206131).
第一作者机构:[1]Hebei Med Univ, Res Ctr, Hosp 4, Shijiazhuang, Hebei, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Hebei Med Univ, Res Ctr, Hosp 4, Shijiazhuang, Hebei, Peoples R China
推荐引用方式(GB/T 7714):
Wei Sisi,Dai Suli,Zhang Cong,et al.LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex[J].FRONTIERS IN ONCOLOGY.2021,11:doi:10.3389/fonc.2021.721604.
APA:
Wei, Sisi,Dai, Suli,Zhang, Cong,Zhao, Ruinian,Zhao, Zitong...&Zhao, Lianmei.(2021).LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex.FRONTIERS IN ONCOLOGY,11,
MLA:
Wei, Sisi,et al."LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex".FRONTIERS IN ONCOLOGY 11.(2021)