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tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming

Bifei Fu1, YuMing Lou1, Xiaofeng Lu1

  • 1Department of Breast and Thyroid Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.

Life Science Alliance
|December 11, 2023
PubMed

Insights

A novel tRNA-derived fragment, tRF-30, is down-regulated in papillary thyroid cancer (PTC). This fragment inhibits PTC cell proliferation and invasion by targeting pyruvate carboxylase, offering a potential therapeutic strategy for PTC.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • tRNA-derived fragments (tRFs) and tRNA-derived small interfering RNAs (tiRNAs) are emerging noncoding RNAs involved in human cancer pathology.
  • The specific roles of tRFs and tiRNAs in papillary thyroid cancer (PTC) development and progression remain largely uncharacterized.

Purpose of the Study:

  • To investigate the biological functions of tRFs and tiRNAs in papillary thyroid cancer.
  • To identify novel molecular mechanisms and potential therapeutic targets in PTC.

Main Methods:

  • Differential expression analysis of tRFs and tiRNAs in PTC tissues and cell lines.
  • Functional assays to assess the impact of tRF-30 on PTC cell proliferation and invasion.
  • Mechanistic studies involving direct binding assays, protein level analysis, and metabolic pathway investigation.

Main Results:

  • A novel 5'tRNA-derived fragment, tRF-1:30-Gly-CCC-3 (tRF-30), was significantly downregulated in PTC tissues and cell lines.
  • tRF-30 demonstrated inhibitory effects on PTC cell proliferation and invasion.
  • tRF-30 was found to directly bind to pyruvate carboxylase (PC), reducing its protein levels and disrupting TCA cycle anaplerosis, thereby impacting metabolic reprogramming in PTC.

Conclusions:

  • tRF-30 represents a novel tumor suppressor in papillary thyroid cancer.
  • The mechanism involves the downregulation of pyruvate carboxylase and subsequent metabolic alterations.
  • tRF-30 presents a potential biomarker and therapeutic target for PTC treatment.

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