PMID- 35526007
OWN - NLM
STAT- MEDLINE
DCOM- 20220510
LR  - 20220716
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 15
IP  - 1
DP  - 2022 May 7
TI  - A novel tRNA-derived fragment AS-tDR-007333 promotes the malignancy of NSCLC via 
      the HSPB1/MED29 and ELK4/MED29 axes.
PG  - 53
LID - 10.1186/s13045-022-01270-y [doi]
LID - 53
AB  - BACKGROUND: Transfer RNA-derived fragments (tRFs) are a new class of small 
      non-coding RNAs. Recent studies suggest that tRFs participate in some 
      pathological processes. However, the biological functions and mechanisms of tRFs 
      in non-small cell lung cancer (NSCLC) are largely unknown. METHODS: 
      Differentially expressed tRFs were identified by tRF and tiRNA sequencing using 9 
      pairs of pre- and post-operation plasma from patients with NSCLC. Quantitative 
      real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used 
      to determine the levels of tRF in tissues, plasma, and cells. Gain- and 
      loss-of-function experiments were implemented to investigate the oncogenic 
      effects of tRF on NSCLC cells in vitro and in vivo. Chromatin immunoprecipitation 
      (ChIP), luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation 
      (RIP), Western blot, co-immunoprecipitation (Co-IP) assays, and rescue 
      experiments were performed to explore the regulatory mechanisms of tRF in NSCLC. 
      RESULTS: AS-tDR-007333 was an uncharacterized tRF and significantly up-regulated 
      in NSCLC tissues, plasma, and cells. Clinically, AS-tDR-007333 overexpression 
      could distinguish NSCLC patients from healthy controls and associated with poorer 
      prognosis of NSCLC patients. Functionally, overexpression of AS-tDR-007333 
      enhanced proliferation and migration of NSCLC cells, whereas knockdown of 
      AS-tDR-007333 resulted in opposite effects. Mechanistically, AS-tDR-007333 
      promoted the malignancy of NSCLC cells by activating MED29 through two distinct 
      mechanisms. First, AS-tDR-007333 bound to and interacted with HSPB1, which 
      activated MED29 expression by enhancing H3K4me1 and H3K27ac in MED29 promoter. 
      Second, AS-tDR-007333 stimulated the expression of transcription factor ELK4, 
      which bound to MED29 promoter and increased its transcription. Therapeutically, 
      inhibition of AS-tDR-007333 suppressed NSCLC cell growth in vivo. CONCLUSIONS: 
      Our study identifies a new oncogenic tRF and uncovers a novel mechanism that 
      AS-tDR-007333 promotes NSCLC malignancy through the HSPB1-MED29 and ELK4-MED29 
      axes. AS-tDR-007333 is a potential diagnostic or prognostic marker and 
      therapeutic target for NSCLC.
CI  - (c) 2022. The Author(s).
FAU - Yang, Wenhan
AU  - Yang W
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Gao, Kaiping
AU  - Gao K
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Qian, Youhui
AU  - Qian Y
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Shenzhen 
      University, 3002 West Shungang Road, Shenzhen, 518035, China.
FAU - Huang, Yongyi
AU  - Huang Y
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Xiang, Qin
AU  - Xiang Q
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Chen, Cheng
AU  - Chen C
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Chen, Qianqian
AU  - Chen Q
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Wang, Yiling
AU  - Wang Y
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Fang, Fuyuan
AU  - Fang F
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Shenzhen 
      University, 3002 West Shungang Road, Shenzhen, 518035, China.
FAU - He, Qihan
AU  - He Q
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Chen, Siqi
AU  - Chen S
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Shenzhen 
      University, 3002 West Shungang Road, Shenzhen, 518035, China.
FAU - Xiong, Juan
AU  - Xiong J
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China.
FAU - Chen, Yangchao
AU  - Chen Y
AD  - Faculty of Medicine, The Chinese University of Hong Kong, Rm508A, Lo Kwee-Seong 
      Integrated Biomedical Sciences Bldg, Shatin, NT, Hong Kong, China.
FAU - Xie, Ni
AU  - Xie N
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Shenzhen 
      University, 3002 West Shungang Road, Shenzhen, 518035, China. xn100@szu.edu.cn.
FAU - Zheng, Duo
AU  - Zheng D
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China. dzheng@szu.edu.cn.
FAU - Zhai, Rihong
AU  - Zhai R
AUID- ORCID: 0000-0003-0631-4134
AD  - School of Public Health, Shenzhen University Health Science Center, 1066 Xueyuan 
      Ave., Shenzhen, 518055, China. rzhai@szu.edu.cn.
AD  - Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, 
      International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 
      China. rzhai@szu.edu.cn.
AD  - Department of Thoracic Surgery, Shenzhen University General Hospital, 1098 
      Xueyuan Ave., Shenzhen, 518055, China. rzhai@szu.edu.cn.
LA  - eng
GR  - 41977372/National Natural Science Foundation of China/
GR  - 81972003/National Natural Science Foundation of China/
GR  - 2017B 030301016/Science and Technology Program of Guangdong Province/
GR  - 2019A1515010210/Natural Science Foundation of Guangdong Province/
GR  - 2021A1515011046/Natural Science Foundation of Guangdong Province/
GR  - 2021A1515012144/Natural Science Foundation of Guangdong Province/
GR  - JCYJ20180507182427559/Shenzhen Science and Technology Innovation Commission/
GR  - JCYJ20170818100842319/Shenzhen Science and Technology Innovation Commission/
GR  - A2018312/Guangdong Medical Research Foundation/
GR  - 86000000210/Shenzhen University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220507
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (ELK4 protein, human)
RN  - 0 (HSPB1 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 146481-62-1 (ets-Domain Protein Elk-4)
RN  - 9014-25-9 (RNA, Transfer)
SB  - IM
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - Gene Expression Regulation
MH  - Heat-Shock Proteins/genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/genetics
MH  - Molecular Chaperones
MH  - RNA, Transfer/genetics/metabolism
MH  - ets-Domain Protein Elk-4/genetics/metabolism
PMC - PMC9077895
OTO - NOTNLM
OT  - AS-tDR-007333
OT  - ELK4
OT  - HSPB1
OT  - MED29
OT  - Non-small cell lung cancer
OT  - tRNA-derived fragments
COIS- The authors declare that they have no competing interests.
EDAT- 2022/05/08 06:00
MHDA- 2022/05/11 06:00
PMCR- 2022/05/07
CRDT- 2022/05/07 23:38
PHST- 2021/12/23 00:00 [received]
PHST- 2022/04/21 00:00 [accepted]
PHST- 2022/05/07 23:38 [entrez]
PHST- 2022/05/08 06:00 [pubmed]
PHST- 2022/05/11 06:00 [medline]
PHST- 2022/05/07 00:00 [pmc-release]
AID - 10.1186/s13045-022-01270-y [pii]
AID - 1270 [pii]
AID - 10.1186/s13045-022-01270-y [doi]
PST - epublish
SO  - J Hematol Oncol. 2022 May 7;15(1):53. doi: 10.1186/s13045-022-01270-y.