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5'-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with

Chengdong Wu1,2,3,4,5,6, Dekai Liu1,2,3,4,5,6, Lufei Zhang1,2,3,4,5,6

  • 1Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

Frontiers of Medicine
|March 27, 2023
PubMed

Insights

A novel tRNA-derived small RNA (tsRNA), 5'-tiRNA-Gln, is downregulated in hepatocellular carcinoma (HCC). This tsRNA inhibits HCC progression by binding EIF4A1, partially blocking translation and impacting key signaling pathways.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • tRNA-derived small RNAs (tsRNAs) are emerging non-coding RNAs implicated in various diseases.
  • The specific role of tsRNAs in hepatocellular carcinoma (HCC) pathogenesis remains largely undefined.

Purpose of the Study:

  • To investigate the expression and function of tsRNAs in HCC.
  • To identify novel tsRNAs that regulate HCC progression.

Main Methods:

  • Differential expression profiling of tsRNAs in HCC tissues.
  • In vitro and in vivo functional assays (overexpression and knockdown) of 5 -tiRNA-Gln.
  • RNA-protein binding assays and mechanistic studies involving EIF4A1 and G-quadruplex structures.
  • Correlation analysis of tsRNA expression with protein levels in HCC tissues.

Main Results:

  • A novel tsRNA, 5 -tiRNA-Gln, derived from tRNA Gln-TTG, was found to be significantly downregulated in HCC.
  • Overexpression of 5 -tiRNA-Gln suppressed HCC cell proliferation, migration, and invasion, while knockdown enhanced these processes.
  • 5 -tiRNA-Gln binds to eukaryotic initiation factor 4A-I (EIF4A1), partially inhibiting translation initiation and downregulating proteins like ARAF, MEK1/2, and STAT3.
  • The G-quadruplex structure within 5 -tiRNA-Gln is critical for its interaction with EIF4A1 and subsequent inhibition of HCC progression.

Conclusions:

  • 5 -tiRNA-Gln acts as a tumor suppressor in HCC by interacting with EIF4A1 via its G-quadruplex structure.
  • This interaction partially inhibits translation, affecting signaling pathways crucial for HCC progression.
  • 5 -tiRNA-Gln represents a potential biomarker and therapeutic target for hepatocellular carcinoma.
Keywords:
EIF4A1G-quadruplexhepatocellular carcinomatRNA-derived small RNAtranslation initiation

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