HNF4A-AS1 inhibits the progression of hepatocellular carcinoma by promoting the ubiquitin-modulated degradation of PCBP2 and suppressing the stability of ARG2 mRNA

作者：Wenbo Jia, Yu Liang, Bin Xu, Yanzhi Feng, Jinyi Wang, Zhu Deming, Chao Xu, Litao Liang, Yongping Zhou, Lianbao Kong, Wenzhou Ding · 发表于：International Journal of Biological Sciences · 年份：2024 · DOI：10.7150/ijbs.95276 · 被引用次数：7 · 研究领域：RNA modifications and cancer、Peptidase Inhibition and Analysis、Signaling Pathways in Disease

functional studies demonstrated that HNF4A-AS1 inhibits the proliferation, invasion, and stemness of HCC cells. Mechanistically, it was observed that HNF4A-AS1 physically interacts with the KH3 domain of PCBP2 through a specific segment (491-672 nt). This interaction facilitates the recruitment of PCBP2 by AIP4, leading to the ubiquitination and subsequent degradation of PCBP2. Furthermore, HNF4A-AS1 was found to regulate the stability of AGR2 mRNA by modulating PCBP2, thereby influencing the malignant phenotype of HCC. Overall, our study demonstrated a positive association between the decrease in HNF4A-AS1 expression and the prognosis of patients with HCC in a clinical setting. HNF4A-AS1 can suppress the stability of ARG2 mRNA by promoting the ubiquitin-modulated degradation of PCBP2, which suppresses HCC progression. HNF4A-AS1 may serve as a potential therapeutic target for HCC.