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1.陆军军医大学(第三军医大学),军事预防医学系军队流行病学教研室,全军呼吸病研究重点实验室,重庆
2.陆军军医大学(第三军医大学),第二附属医院呼吸内科研究所,全军呼吸病研究重点实验室,重庆
李亚斐, E-mail: liyafei2008@hotmail.com
纸质出版日期:2025-01-30,
收稿日期:2024-08-15,
修回日期:2024-10-21,
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陆春利, 单亦凡, 谢薇佳, 等. 肺腺癌相关tsRNA的筛选和验证[J]. 陆军军医大学学报, 2025,47(2):122-131.
LU CHUNLI, SHAN YIFAN, XIE WEIJIA, et al. Screening and validation of tsRNAs associated with lung adenocarcinoma. [J]. Journal of army medical university, 2025, 47(2): 122-131.
陆春利, 单亦凡, 谢薇佳, 等. 肺腺癌相关tsRNA的筛选和验证[J]. 陆军军医大学学报, 2025,47(2):122-131. DOI: 10.16016/j.2097-0927.202408059.
LU CHUNLI, SHAN YIFAN, XIE WEIJIA, et al. Screening and validation of tsRNAs associated with lung adenocarcinoma. [J]. Journal of army medical university, 2025, 47(2): 122-131. DOI: 10.16016/j.2097-0927.202408059.
目的
2
通过分析tsRNA在肺腺癌中的差异表达情况及其表达水平与患者预后的关系,进一步筛选并验证肺腺癌相关tsRNA,以了解其在肺腺癌发生和进展中的相关机制。
方法
2
基于计算医学中心数据库筛选出在肺腺癌组织和正常组织中差异表达的tsRNA;基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析tsRNA表达水平对肺腺癌患者预后的影响;基于TRFtarget2.0和tRFTar数据库预测靶基因;基于DAVID、KOBA KEGG在线网站进行基因本体论(Gene Ontology,GO)富集分析和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析;基于阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham CANcer data analysis Portal,UALCAN)分析靶基因在肺腺癌组织和正常组织中的表达水平。采用增殖实验、迁移实验、侵袭实验验证tRF-19-69M8LOJX在肺腺癌细胞中的生物学功能。
结果
2
与正常组织相比,tRF-19-69M8LOJX在肺腺癌组织中表达上调(log
2
FC=4.28,FDR
<
0.05)。高表达水平的tRF-19-69M8LOJX预示着更短的无进展生存期(
HR
=1.565,95%
CI
=1.142~2.145,
P
=0.005);过表达tRF-19-69M8LOJX促进A549细胞的增殖、迁移(
P
<
0.001)和侵袭(
P
=0.009);COL1A1(
P
=0.002)和VCAN(
P
=0.022)在tRF-19-69M8LOJX过表达细胞模型中显著上调。
结论
2
tRF-19-69M8LOJX在肺腺癌组织的表达水平上调,与患者不良预后密切相关,可能在肺腺癌的发生发展中起着重要作用。
Objective To explore the roles of transfer RNA-derived small RNAs (tsRNAs) in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma. Methods The
differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center. The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas (TCGA) database (TCGA-LUAD). The target genes were predicted based on TRFtarget2.0 and tRFTar databases. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed based on DAVID and KOBA KEGG online websites. The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) database.
In vitro
cell proliferation, migration, and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues, tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues (log
2
FC=4.28, FDR
<
0.05). High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival (
HR
=1.565, 95%
CI
=1.142-2.145,
P
=0.005). And its overexpression promoted cell proliferation and migration (
P
<
0.001), and invasion (
P
=0.009) of A549 cells, and up-regulated COL1A1 (
P
=0.002) and VCAN (
P
=0.022) significantly in the tRF-19-69M8LOJX overexpression cell model. Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues. And its high expression is closely associated with poor prognosis. The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.
转移RNA衍生的小RNA肺腺癌预后
transfer RNA-derived small RNAlung adenocarcinomaprognosis
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