METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN
RNA methylation is emerging as an important regulator of gene expression. Dysregulation of methyltransferase that is essential for RNA modification contributes to the development and progression of human cancers. Here we show that methyltransferase-like 1 (METTL1) is upregulated in hepatocellular carcinoma (HCC) and exhibits oncogenic activities via PTEN/AKT signaling pathway. High expression of METTL1 is correlated with larger tumor size, higher serum AFP level, tumor vascular invasion, and poor prognosis in two independent cohorts containing 892 patients with HCC. Multivariate analyses suggest METTL1 as an independent factor for unfavorable overall survival. In vitro studies demonstrate that METTL1 overexpression promotes cell proliferation and migration, whereas its knockdown results in opposite phenotypes. Gene set enrichment analysis (GSEA) indicates PTEN pathway is activated in patients with low METTL1 expression. Ectopic expression of PTEN or inhibition of AKT activity significantly attenuates the METTL1-mediated malignant phenotypes. In clinical samples, METTL1 expression is reversely associated with PTEN expression. Combination of low METTL1 expression and high PTEN expression is significantly correlated with overall survival, more so than either METTL1 or PTEN expression alone. Collectively, our data suggest that METTL1 serves as a promising prognostic biomarker and that targeting METTL1/PTEN axis may provide therapeutic potential in HCC intervention.
METTL1 is upregulated in HCC and correlated with poor outcomes.
METTL1 promotes cell proliferation and migration in HCC.
METTL1 exerts oncogenic activities via suppression of PTEN signaling.
KeywordsMETTL1 PTEN Prognosis Hepatocellular carcinoma
The study was supported by the National Natural Science Foundation of China (No. 81960441).
Compliance with ethical standards
Written informed consent was obtained from all patients involved in this study. The use of tissues in this study has been approved by the Institute Research Medical Ethics Committees of SYSUCC and The First Affiliated Hospital of Nanchang University.
Conflict of interest
The authors declare that they have no conflict of interest.
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