A 5 '-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer
Han, Litao1,2; Lai, Hejing3,4; Yang, Yichen1,2; Hu, Jiaqian1,2; Li, Zhe2,5; Ma, Ben1,2; Xu, Weibo1,2; Liu, Wanlin1,2; Wei, Wenjun1,2; Li, Duanshu1,2
2021-07-05
发表期刊JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
EISSN1756-9966
卷号40期号:1
DOI10.1186/s13046-021-02024-3
摘要BackgroundtRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive.MethodsPapillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed.ResultsHerein, we have identified a 33nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent.ConclusionsOur study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.
关键词tiRNA-Gly RBM17 Alternative splicing MAP4K4 Papillary thyroid carcinoma
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收录类别SCIE
语种英语
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000672440300001
出版者BMC
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127818
专题生命科学与技术学院_特聘教授组_翟琦巍组
通讯作者Wang, Yu; Zhai, Qiwei; Ji, Qinghai; Liao, Tian
作者单位1.Fudan Univ, Shanghai Canc Ctr, Dept Head & Neck Surg, Shanghai 200032, Peoples R China;
2.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China;
3.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Ctr Excellence Mol Cell Sci,CAS Key Lab Nutr, Shanghai 200031, Peoples R China;
4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200093, Peoples R China;
5.Fudan Univ, Shanghai Canc Ctr, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai 200032, Peoples R China
通讯作者单位生命科学与技术学院
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Han, Litao,Lai, Hejing,Yang, Yichen,et al. A 5 '-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2021,40(1).
APA Han, Litao.,Lai, Hejing.,Yang, Yichen.,Hu, Jiaqian.,Li, Zhe.,...&Liao, Tian.(2021).A 5 '-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,40(1).
MLA Han, Litao,et al."A 5 '-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 40.1(2021).
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