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Updated: Aug 6, 2026
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Circulating NSUN6 serves as a prognostic biomarker for early metastasis in HCC via hippo pathway modulation
Xutong Li1,2, Honghai Xu3, Yu Chang4
1Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Infectious Diseases, Hefei, 230027, China.
Background:
Portal vein tumor thrombus is a lethal complication of HCC for which effective biomarkers are urgently needed.
Methods:
Through proteomic profiling, functional and mechanistic assays, and machine learning-based evaluation of serum NSUN6 in 472 HCC patients with external validation (n = 98), we characterized an epitranscriptomic regulator of HCC metastasis.
Results:
NSUN6 was downregulated in PVTT and suppressed metastasis by catalyzing m⁵C modification of SAV1 mRNA, stabilizing its transcript and activating Hippo signaling. Furthermore, NSUN6 was released from HCC cells via extracellular vesicle-associated and non-canonical pathways. Circulating NSUN6 levels were inversely associated with metastasis in both discovery and validation cohorts, and lower levels predicted shorter metastasis-free survival.
Conclusion:
Our findings establish the NSUN6-SAV1-YAP axis as a key epitranscriptomic tumor-suppressive mechanism and support circulating NSUN6 as a potential biomarker for early risk stratification in HCC.
