The tRNA-Cys-GCA Derived tsRNAs Suppress Tumor Progression of Gliomas via Regulating VAV2

作者全名："Ren, Jian; Wu, Xiaoling; Shang, Fei-Fei; Qi, Yingqiang; Tang, Zhurong; Wen, Chunjie; Cao, Weiguo; Cheng, Quan; Tan, Lihong; Chen, Huan; Zhou, Hong-Hao; Zou, Hecun"

作者地址："[Ren, Jian; Wu, Xiaoling; Shang, Fei-Fei; Qi, Yingqiang; Tang, Zhurong; Wen, Chunjie; Cao, Weiguo; Chen, Huan; Zhou, Hong-Hao; Zou, Hecun] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Ren, Jian; Tan, Lihong] Chongqing Med & Pharmaceut Coll, Affiliated Hosp, Dept Neurol, Chongqing 401331, Peoples R China; [Wu, Xiaoling] Chongqing Univ Canc Hosp, Chongqing 400030, Peoples R China; [Cheng, Quan; Zhou, Hong-Hao] Cent South Univ, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China"

通信作者："Zou, HC (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China."

来源：DISEASE MARKERS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000890397600001

JCR分区：Q3

影响因子：3.464

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The tsRNAs (tRNA-derived small RNAs) are new types of small noncoding RNAs derived from tRNAs. Gliomas are well-known malignant brain tumors. The study focused on tsRNA characterizations within gliomas. Datasets processing, bioinformatics analyses, and visualizations were performed with the packages of Python and R. Cell proliferations were demonstrated via CCK8 assays and colony formation assays, and in vivo xenograft experiments. Dual-luciferase reporter assay was performed to confirm the binding of tsRNA with its targets. Via using bioinformatics approaches, the hundreds of tsRNAs with available expression abundance were identified in gliomas dataset, most of them derived from D-loop or T-loop fragments of tRNAs. Among tsRNAs derived from tRNA-Cys-GCA, tRFdb-3003a and tRFdb-3003b (tRFdb-3003a/b) were remarkably down-regulated in gliomas. The survival outcome of gliomas patients with low tRFdb-3003a/b expressions was notably worse than that of high-expression patients. In glioma cells, tRFdb-3003a could suppress cells proliferation and colony formation ability. In vivo, tRFdb-3003a suppressed the tumor growth of xenograft gliomas. Enrichment analyses displayed the tRFdb-3003a-related mRNAs were enriched in the specific GO terms, spliceosome and autophagy pathways, and three GSEA molecular signatures. Mechanically, 3'-UTR regions of VAV2 mRNA were predicted to contain the binding positions of tRFdb-3003a/b, tRFdb-3003a and tRFdb-3003b was effective to reduce the relative luciferase activity of cells with VAV2 wild-type reporter. Overexpression of tRFdb-3003a/b could down-regulated the expression levels of VAV2 protein and mRNA in glioma cells. The tRNA-Cys-GCA derived tRFdb-3003a and tRFdb-3003b might act as key player in tumor progressions of gliomas; tRFdb-3003a/b might directly bind to VAV2 and regulate VAV2 expressions in gliomas."

基金机构："National Natural Science Foundation of China; Natural Science Foundation of Chongqing, China; Project of Science and Technology Research Program of Chongqing Education Commission of China; [82003854]; [cstc2021jcyj-msxmX0302]; [KJQN202200430]"

基金资助正文："Acknowledgments This work was supported by grants from the National Natural Science Foundation of China (No. 82003854), and sponsored by the Natural Science Foundation of Chongqing, China (cstc2021jcyj-msxmX0302), and supported by the Project of Science and Technology Research Program of Chongqing Education Commission of China (No. KJQN202200430). Thanks very much to all researcher who have contributed to this work, including Zhurong Tang, Weiguo Cao, Bing Xu, Chunjie Wen, Jiao Pei, Jian Liang, Lihong Tan, Huan Chen, and Yubo Xiong."