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m6A modification-mediated lncRNA UNC5B-AS1 enhances HCC progression through miR-760/IL6 axis.

Li-Ping Yu¹, Sheng-Yu Huang², Kun-Peng Li³

¹Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111, Xianxia Road, Shanghai, 200336, China.

Scientific Reports

|May 24, 2026

Summary

WT1-associated protein (WTAP) enhances the stability and expression of long noncoding RNA UNC5B-AS1 via m6A modification, promoting hepatocellular carcinoma (HCC) progression. This axis also involves sponging miR-760 to upregulate IL6, offering potential therapeutic targets for HCC.

Keywords:

Hepatocellular carcinoma (HCC)IL6 N6-methyladenosine UNC5B-AS1 WTAP

Related Experiment Videos

Area of Science:

Molecular Biology
Oncology
Epigenetics

Background:

Hepatocellular carcinoma (HCC) is a significant global health concern.
Long noncoding RNAs (lncRNAs) like UNC5B-AS1 are implicated in cancer progression.
The role of the WT1-associated protein (WTAP)/UNC5B-AS1 axis in HCC remains largely undefined.

Purpose of the Study:

To elucidate the precise roles and mechanisms of the WTAP/UNC5B-AS1 axis in hepatocellular carcinoma (HCC) progression.
To investigate the impact of m6A modification on UNC5B-AS1 stability and expression in HCC.
To identify potential therapeutic strategies targeting the m6A-RNA regulatory pathway in HCC.

Main Methods:

Analysis of m6A modification sites on UNC5B-AS1.
Assessment of WTAP's effect on UNC5B-AS1 stability and expression using m6A reader YTHDF1.
Functional assays to evaluate the role of the WTAP/UNC5B-AS1 axis in HCC progression.
Investigation of the interaction between UNC5B-AS1, hsa-miR-760, and Interleukin-6 (IL6) using molecular sponge assays.

Main Results:

High abundance of m6A modification sites was observed on UNC5B-AS1 in HCC.
WTAP was found to enhance UNC5B-AS1 stability and expression through m6A reader YTHDF1.
The WTAP/UNC5B-AS1 axis was demonstrated to drive HCC progression.
UNC5B-AS1 functions as a molecular sponge for hsa-miR-760, leading to increased IL6 expression and promoting HCC progression.

Conclusions:

The WTAP/UNC5B-AS1 axis, regulated by m6A modification, plays a crucial role in promoting HCC progression.
UNC5B-AS1 contributes to HCC advancement by sponging hsa-miR-760 and upregulating IL6.
This study reveals a novel m6A-RNA regulatory mechanism with potential for developing therapeutic strategies against HCC.