Targeted Eicosanoid Profiling Reveals MicroRNA-155 Shifts PGE2/PGD2 Balance Towards Oncogenic State
Kim, S.; Lee, E. S.; Lee, E. J.; Jung, J. Y.; Lee, S. B.; Lee, H. J.; Kim, J.; Kim, H. J.; Lee, J. W.; Son, B. H.; Gong, G.-Y.; Ahn, S.-H.; Chang, S.
Show abstract
microRNA-155 is a strong oncogenic microRNAs with multiple functions. To reveal its novel function in cancer metabolism, we performed a targeted metabolomic analysis of icosanoids, the key metabolites of inflammation-related carcinogenesis. We found miR-155-depleted cells expressed unbalanced prostaglandins, especially in PGE2 and PGD2. Subsequent analysis of primary cancer cells and 20 TNBC specimen indicated a positive correlation between miR-155 and PGE2/PGD2 ratio. Mechanistically, miR-155 controls the prostaglandin shift by up-regulating PGE2-producing enzymes PTGES/PTGES2 and down-regulating PGD2-producing enzyme PTGDS. Further analysis showed that the up-regulation of PTGES2 is driven by miR-155-cMYC axis whereas PTGES is transactivated by miR-155-KLF4 axis, indicating a dual-regulatory mode for the metabolic enzyme expression drives a shift in PGE2/PGD2 balance. Lastly, we show the miR-155-driven cellular proliferation is significantly restored by the siRNA of PTGES1/2, of which expression also correlates with patients survival. Taken altogether, our study reveals an unprecedented oncogenic function of miR-155 on prostaglandin regulation.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer 95%
- A positive feedback loop between ZEB2 and ACSL4 regulates lipid metabolism to promote breast cancer metastasis 94%
- Fibroblast activation during decidualization: Embryo-derived TNFα induction of PGI2-PPARδ-ACTIVIN A pathway through luminal epithelium 94%
Similar papers in this journal
- Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A 94%
- Systematic analysis of aberrances of ferroptosis reveals its potential functional roles in cancer 93%
- Identification of S1PR4 as an immune modulator for favourable prognosis in HNSCC through unbiased machine learning 92%
Similar papers in this journal
- Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma 92%
- Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition 91%
- Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury 91%
Similar papers in this journal
Similar papers in this journal
- PRMT1 regulates EGFR and Wnt signaling pathways and is a promising target for combinatorial treatment of breast cancer 92%
- Epigenetic Modulation of SPCA2 Reverses Epithelial to Mesenchymal Transition in Breast Cancer Cells 92%
- Oncogenic EFNA4 amplification promotes lung adenocarcinoma lymph node metastasis 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.