Recent Publications Harnessing the Power of Translatomics

Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.

In this week’s Sunday papers,

  • Tan et al. highlight a causal role of diabetes in worsening breast cancer outcomes and suggest FIBCD1 as a promising therapeutic target.
  • Wang et al. (2025) underline that NSUN2 drives codon-biased translation to support glycolysis and progression in triple-negative breast cancer.
  • Wang et al. (2024) identify how disrupted tRNA modifications directly influence codon–ribosome interactions, fueling metabolic reprogramming and malignancy.

Diabetes is causally associated with increased breast cancer mortality by inducing FIBCD1 to activate MCM5-mediated cell cycle arrest via modulating H3K27ac

Cell Death & Disease. 2025.

Tan, B., Liu, Y., Chen, Q., Yang, W., Yang, W., Gao, K., Fu, L., Zhang, T., Chen, P., Huang, Y. and Wang, Y.

Sunday Paper 1

This study establishes a causal link between diabetes and increased breast cancer mortality using multiple advanced causal inference models, including g-computation, inverse probability of treatment weighting (IPTW), targeted maximum likelihood estimation (TMLE), and TMLE-super learner.

Using these models, Tan et al. demonstrate that among 3,386 breast cancer patients, five-year mortality odds are significantly elevated in those diagnosed with diabetes, with an adjusted odds ratio (OR) between ~1.9 and ~2.3. Hyperglycemia upregulates FIBCD1 gene in tumour tissues and in breast cancer cells cultured under high glucose. Elevated FIBCD1 promotes proliferation, migration, and invasion, while its knockdown suppresses tumour growth in diabetic mouse models.

Through combined RNA-seq and Ribo-seq, MCM5 was identified as a translational and transcriptional target of FIBCD1. FIBCD1 enhances histone H3K27 acetylation (H3K27ac) level at the MCM5 promoter via the PDH–acetyl-CoA axis, driving S-phase cell cycle arrest. These findings support a causal role of diabetes in worsening breast cancer outcomes and suggest FIBCD1 as a promising therapeutic target in this context.

Learn more about EIRNABio’s ribosome profiling services here.

NSUN2–tRNAⱽᵃˡ⁻ᶜᴬᶜ-axis-regulated codon-biased translation drives triple-negative breast cancer glycolysis and progression

Cellular & Molecular Biology Letters. 2025.

Wang, W., Ding, Y., Zhao, H., Wang, S., Huang, J. and Sun, L.

Sunday Paper 2

In triple-negative breast cancer (TNBC), the RNA methyltransferase NSUN2 is significantly upregulated and correlates with worse patient outcomes. Using tRNA m⁵C bisulfite sequencing and tRNA-seq, the authors found that NSUN2 specifically mediates 5-methylcytosine (m⁵C) modification on tRNAVal-CAC. Ribo-seq and polysome profiling then showed that this modification selectively enhances translation of glycolysis-related proteins in a codon-frequency-dependent manner particularly in transcripts enriched in Val-GUG codons, such as HK1, PFKM, ALDH3A2 and ALDH7A1,  which shift toward heavier polysome fractions when NSUN2 was active.

Loss of NSUN2 or disruption of this modification impairs translation of these metabolic enzymes, suppresses glycolysis, and significantly limits TNBC cell proliferation, migration, and invasion in both in vitro assays and in vivo xenograft models. Additionally, overexpression of NSUN2 confers resistance to the chemotherapy agent docetaxel, whereas its downregulation sensitizes TNBC cells to treatment. From a clinical perspective, NSUN2 and glycolysis-related genes are elevated in docetaxel-resistant TNBC tissues, further underscoring NSUN2’s role in metabolic reprogramming and chemoresistance.

Collectively, this study unveils a novel NSUN2– tRNAVal-CAC axis that drives codon-biased translation of glycolytic genes to fuel TNBC progression and chemoresistance, positioning NSUN2 as a promising prognostic biomarker and therapeutic target in this aggressive cancer subtype.

Learn more about EIRNABio’s ribosome profiling, tRNA-seq, and polysome profiling services here.

Downregulation of tRNA methyltransferase FTSJ1 by PM2. 5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation

Cell Death & Disease. 2024.

Wang, Y., Wen, Y., Chen, Q., Huang, Y., Zhou, D., Yang, W., Yang, L., Xiong, J., Gao, K., Sun, L. and Zhai, R.

Sunday Paper 3

Fine particulate matter (PM2.5) exposure is epidemiologically linked to increased lung cancer risk, but its molecular mechanisms were previously unclear. In this study, the authors found that PM2.5 suppresses the expression of the tRNA methyltransferase FTSJ1, leading to reduced 2ʹ-O-methyladenosine modifications on tRNA both in vitro and in vivo. Loss of FTSJ1 enhances glycolytic metabolism in non-small cell lung cancer (NSCLC) cells, as indicated by elevated lactate, pyruvate, and extracellular acidification rate; these effects are reversed by 2-deoxy-D-glucose, confirming glycolysis dependence.

Using Ribo-seq, polysome profiling and RNA-seq data the authors showed that FTSJ1 downregulation increases the expression and translation of PGK1, a key glycolytic enzyme. Conversely, overexpression of FTSJ1 suppresses both PGK1 mRNA and protein levels and dampens glycolysis and proliferation. Clinically, FTSJ1 levels inversely correlate with PGK1 expression and PET/CT SUVmax—a marker of glucose uptake—in NSCLC tumor samples.

In summary, PM2.5-driven downregulation of the tRNA-modifying enzyme FTSJ1 fosters glycolytic reprogramming and malignancy in NSCLC via facilitating PGK1 translational activation. Restoring or enhancing FTSJ1 activity may offer a novel therapeutic strategy against NSCLC, particularly in contexts of environmental pollutant exposure.

Learn more about EIRNABio’s ribosome profiling and polysome profiling services here.