Circulating NSUN6 serves as a prognostic biomarker for early metastasis in HCC via hippo pathway modulation.

Authors

Xutong Li, Honghai Xu, Yu Chang, Yani Zhang, Hui Xu, Xin Yin, Wanxiang Zhang, Yi Luo, Wanting Lu, Wenhu Fan, Wanwan Ruan, Jiapei Shen, Zhenxing Li, Shucheng Du, Lutterodt Bentum-Ennin, Jing Ni, Wei Gao, Jiabin Li, Wanglai Hu, Wanshui Yang, Yufeng Gao, Hao Gu

Published in

Journal of experimental & clinical cancer research : CR. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Portal vein tumor thrombus is a lethal complication of HCC for which effective biomarkers are urgently needed.
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.
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.
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.

PMID:
42464346
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.