5′-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I

doi:10.1007/s11684-022-0966-6

Frontiers of Medicine

2023, Vol. 17

Issue (3): 476-492 https://doi.org/10.1007/s11684-022-0966-6

本期目录

5′-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I

Chengdong Wu, Dekai Liu, Lufei Zhang, Jingjie Wang, Yuan Ding, Zhongquan Sun, Weilin Wang(

)

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China; Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China; Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, China; Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China; Cancer Center, Zhejiang University, Hangzhou 310009, China

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Abstract：

tRNA-derived small RNAs (tsRNAs) are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases. However, their exact presence and function in hepatocellular carcinoma (HCC) remain unclear. Here, differentially expressed tsRNAs in HCC were profiled. A novel tsRNA, tRNA^Gln-TTG derived 5′-tiRNA-Gln, is significantly downregulated, and its expression level is correlated with progression in patients. In HCC cells, 5′-tiRNA-Gln overexpression impaired the proliferation, migration, and invasion in vitro and in vivo, while 5′-tiRNA-Gln knockdown yielded opposite results. 5′-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I (EIF4A1), which unwinds complex RNA secondary structures during translation initiation, causing the partial inhibition of translation. The suppressed downregulated proteins include ARAF, MEK1/2 and STAT3, causing the impaired signaling pathway related to HCC progression. Furthermore, based on the construction of a mutant 5′-tiRNA-Gln, the sequence of forming intramolecular G-quadruplex structure is crucial for 5′-tiRNA-Gln to strongly bind EIF4A1 and repress translation. Clinically, 5′-tiRNA-Gln expression level is negatively correlated with ARAF, MEK1/2, and STAT3 in HCC tissues. Collectively, these findings reveal that 5′-tiRNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.

Key words： EIF4A1 G-quadruplex hepatocellular carcinoma tRNA-derived small RNA translation initiation

收稿日期: 2022-06-27 出版日期: 2023-07-28

Corresponding Author(s): Weilin Wang

引用本文:

. [J]. Frontiers of Medicine, 2023, 17(3): 476-492.
Chengdong Wu, Dekai Liu, Lufei Zhang, Jingjie Wang, Yuan Ding, Zhongquan Sun, Weilin Wang. 5′-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I. Front. Med., 2023, 17(3): 476-492.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-022-0966-6
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I3/476

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