Cell death & diseaseJul 17, 2026

LARS controls aging and self-cleaning processes in liver cancer cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 18, 2026

Abstract

High levels of human leucyl-tRNA synthetase (LARS) in liver cancer are associated with poor clinical outcomes.

LARS functions as a nutrient sensor and regulates cell growth independently of its role in protein synthesis.
Knockdown of LARS in liver cancer cells reduces cell proliferation and growth, while promoting cell migration.
Differential gene expression analysis shows significant clustering of genes in the cellular senescence pathway following LARS knockdown.
Increased levels of p21 and p16, along with heightened senescence-associated β-galactosidase activity, are observed in LARS-deficient cells.
LARS depletion triggers autophagy and oxidative stress, characterized by elevated reactive oxygen species and reduced mitochondrial membrane potential.
Re-expression of LARS can largely reverse the senescence, autophagy, and oxidative stress effects caused by its knockdown.

Simplified

Human cytoplasmic leucyl-tRNA synthetase (LARS) is known to catalyze the ligation of leucine to tRNA^Leu during protein biosynthesis. However, LARS also acts as a nutrient sensor in a non-canonical activity to regulate cell growth. In this investigation, LARS was determined to be expressed at high levels in human liver cancer, which correlated with poor clinical outcomes in patients. Knockdown of LARS in HepG2 liver cancer cells suppressed cell proliferation and growth, yet promoted cell migration, without affecting global protein translation. Using data from RNA sequencing, differentially expressed genes in response to LARS knockdown were significantly clustered in the cellular senescence pathway. Elevated p21 and p16 expression with increased senescence-associated β-galactosidase activity was observed in LARS knockdown HepG2 cells. In addition, autophagy with increasing autophagic flux was triggered in LARS knockdown HepG2 cells. Furthermore, the depletion of LARS induced oxidative stress with increased production of reactive oxygen species and decreased mitochondrial membrane potential. Importantly, re-expression of shRNA-resistant LARS largely rescued the senescence, autophagy, and oxidative stress caused by LARS knockdown, confirming the specificity of these effects. These findings suggest that LARS plays a role in regulating liver cancer cell proliferation via multiple cellular responses and may serve as a promising therapeutic target in liver cancer.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

0%of authors

0 of 5

authors report competing interests

5 report none

PubMed

LARS controls aging and self-cleaning processes in liver cancer cells

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief