5'-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I / 医学前沿

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, tRNAGln-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'-tiRJNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.

Study on sodium aescinate inhibiting hepatocellular carcinoma by eif4a1 / 中国药理学通报

Aim To investigate the correlation between the expression of EIF4A1 and hepatocellular carcinoma (HCC) and the potential mechanism of sodium aescinate inhibiting the proliferation of hepatoma cell lines. Methods Immunohistochemistry was used to detect the expression level of EIF4A1 in tumor specimens of 80 patients with HCC. The results combined with clinical indicators and follow-up information were used to analyze their relevance. Annexin V-FITC/PI double staining method was employed to detect the effects of sodium aescinate on apoptosis of HepG2 and human L02 cell lines. Transwell migration assay was used to detect the effect of sodium aescinate on the migration of two cell lines. Western blot, qPCR and immunofluorescence were used to detect the expression changes of E1F4A1 of two cell lines after sodium aescinate treat ment. Results The expression of EIF4A1 significantly increased in HCC tissues, and the expression of EIF4A1 was correlated with tumor differentiation, tumor diameter and survival time. Sodium aescinate (40 jxmol • L"1) could significantly promote the apoptosis of liver cancer cell line and inhibit its migration a-bility, but had no effect on normal liver cell line. Sodium aescinate inhibited the growth and proliferation of hepatoma cell line while down-regulated the expression of hepatoma cell line EIF4A1. Conclusions EIF4A1 is associated with the development of HCC, and sodium aescinate can inhibit hepatoma cell line via affecting the expression of EIF4A1.