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Targeting mitochondrial tyrosyl-tRNA synthetase YARS2 suppresses colorectal cancer progression

Qingxia Fang1, Jingyang Lin2, Liang Gao3

  • 1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou 310014, China.

Cancer Biology & Therapy
|September 26, 2022
PubMed

Insights

Mitochondrial tyrosyl-tRNA synthetase YARS2 is upregulated in colorectal cancer. Inhibiting YARS2 suppresses tumor growth and migration, suggesting YARS2 as a potential therapeutic target for colorectal cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Transfer RNA (tRNA) dysregulation is implicated in tumorigenesis, including colorectal cancer.
  • Mitochondrial tyrosyl-tRNA synthetase (YARS2) plays a crucial role in tRNA synthesis and function.

Purpose of the Study:

  • To investigate the role of YARS2 in colorectal cancer progression.
  • To evaluate YARS2 as a potential therapeutic target.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) to measure YARS2 mRNA levels in tumor and normal tissues.
  • YARS2 knockdown in SW620 colon cancer cells.
  • Assessment of cell proliferation, migration, tRNATyr levels, oxygen consumption rate (OCR), ATP synthesis, and reactive oxygen species (ROS).

Main Results:

  • YARS2 mRNA expression is significantly higher in colorectal cancer tissues than in normal tissues.
  • YARS2 knockdown inhibited cell proliferation and migration in SW620 cells.
  • YARS2 inhibition decreased tRNATyr levels, OCR, ATP synthesis, and increased ROS, sensitizing cells to 5-FU treatment.

Conclusions:

  • Targeting YARS2 can inhibit colorectal cancer progression.
  • YARS2 is a potential carcinogenesis candidate gene and a promising therapeutic target for colorectal cancer.
Keywords:
YARS2colorectal cancermitochondrialreactive oxygentyrosyl-tRNA

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