What question did this study set out to answer?

To identify the m6A-mRNA modification landscape in hepatocellular carcinoma and characterize the functional consequences of YTHDF2 downregulation on tumor progression.

November 18, 2019Molecular CancerOpen Access

YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma

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To identify the m6A-mRNA modification landscape in hepatocellular carcinoma and characterize the functional consequences of YTHDF2 downregulation on tumor progression.
Quantified m6A-mRNA modifications in human hepatocellular carcinoma tissues using liquid chromatography-tandem mass spectrometry and m6A immunoprecipitation sequencing.
Evaluated oncogenic phenotypes following YTHDF2 knockdown in human liver cancer cells and conditional knockout in mouse hepatocytes.
Tested pharmacological rescue of the YTHDF2 pathway using the selective hypoxia-inducible factor-2α antagonist PT2385.
Human hepatocellular carcinoma tissues exhibited an overall gain of m6A-modified transcripts driven by reduced YTHDF2 expression, which correlated with poor patient prognosis.
Loss of YTHDF2 prevented normal degradation of m6A-tagged IL11 and SERPINE2 transcripts, triggering severe inflammation, disrupted vascular normalization, and metastasis.
Pharmacological inhibition of HIF-2α by PT2385 restored YTHDF2 expression and suppressed liver tumor progression in preclinical models.

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Implication

Translational study reveals that YTHDF2 depletion drives inflammation and vascular remodeling in liver cancer, highlighting a targetable epitranscriptomic mechanism.

Cite This Study

Hou et al. (2019) studied this question.

synapsesocial.com/papers/69d9dacf0f32475823a3c963 https://doi.org/10.1186/s12943-019-1082-3

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Implication

Translational study reveals that YTHDF2 depletion drives inflammation and vascular remodeling in liver cancer, highlighting a targetable epitranscriptomic mechanism.

YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma

Key Points

Discussion

Implication

Cite This Study

YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma

Key Points

Discussion

Implication

Cite This Study

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