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Contribution of miRNAs, tRNAs and tRFs to Aberrant Signaling and Translation Deregulation in Lung Cancer

Ilias Skeparnias1, Dimitrios Anastasakis1,2, Katerina Grafanaki1,3

  • 1Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece.

Cancers
|October 23, 2020
PubMed

Insights

This study reveals how microRNAs (miRNAs) and tRNA-derived fragments (tRFs) in lung cancer influence oncogenic signaling and protein translation. Aberrant expression of these non-coding RNAs correlates with altered signaling pathways and increased protein synthesis in cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genomics

Background:

  • MicroRNAs (miRNAs), transfer RNAs (tRNAs), and tRNA-derived fragments (tRFs) are investigated as potential cancer biomarkers.
  • The combined regulatory effect of these non-coding RNAs on oncogenic signaling and translation remains understudied.

Purpose of the Study:

  • To investigate the role of miRNAs and tRFs in lung cancer by analyzing their targets in gene networks.
  • To explore the differential expression of tRNAs and related genes in lung carcinogenesis.
  • To elucidate the impact of specific tRFs on signaling and translation pathways in lung adenocarcinoma cells.

Main Methods:

  • Analysis of miRNA and tRF expression profiles in lung cancer biopsies.
  • Next-generation sequencing (NGS) after transfection of lung adenocarcinoma cells with identified tRFs.
  • Examination of signaling pathways (PI3K/AKT, MAPK) and translation factors (eIF4E, eEF2) in biopsy specimens.
  • Polysome profiling and 48S pre-initiation complex reconstitution experiments.

Main Results:

  • miRNAs and tRFs target gene networks involved in cell proliferation, transcription, and translation regulation.
  • Differential expression of tRNAs and tRNA-related genes suggests their involvement in lung carcinogenesis.
  • Transfection with tRFs identified targets mediating signaling and translation.
  • Crosstalk between PI3K/AKT and MAPK pathways, with downstream activation of eIF4E and eEF2, was observed.
  • Increased global translation rates and aberrant expression of translation initiation factors indicate elevated protein synthesis.

Conclusions:

  • Regulatory non-coding RNAs, including miRNAs and tRFs, modulate signaling and translation pathways in lung cancer.
  • Aberrant expression patterns of these RNAs correlate with deregulation of signaling and translation, contributing to tumorigenesis.
  • These findings highlight the potential of miRNAs and tRFs as therapeutic targets in lung cancer.
Keywords:
lung cancermiRNAssignalingtRFstRNAstranslation

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