Wang Yun-Bing, Salameen Haitham, Hu Yi-Yu, Zhou Shi-Ji, Gong Jun-Hua
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
The Second Clinical College, Chongqing Medical University, Chongqing, 400016, China.
Curr Cancer Drug Targets. 2025;25(6):665-679. doi: 10.2174/0115680096310229240626102449.
This study aims to understand the role of cirrhosis in promoting hepatocellular carcinoma (HCC) progression by analyzing the differential expression of long noncoding RNAs (lncRNAs) between cirrhotic hepatocellular carcinoma (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC).
A transcriptional profile array was used to identify differentially expressed lncRNAs. Subsequently, a specific lncRNA was selected to evaluate the clinical significance, potential functions, regulatory targets, and pathways through both and experiments.
The study identified a lncRNA, which we termed DERCNC, an acronym for Differentially Expressed RNA between Cirrhotic and Non-Cirrhotic HCC. DERCNC was significantly more highly expressed in CHCC than in NCHCC. Clinically, elevated levels of DERCNC expression were positively correlated with both the cirrhotic state and tumor stage and inversely correlated with tumor differentiation. Furthermore, high expression of DERCNC was associated with a poor prognosis for patients. Conditioned medium from the hepatic stellate cell (LX2) was found to enhance DERCNC expression, SOX9 expression, and tumor proliferation. Overexpression of DERCNC similarly promoted tumor proliferation and increased SOX9 levels. Conversely, DERCNC silencing resulted in the opposite effects. Moreover, the pro-proliferative function of DERCNC was reversible through the modulation of SOX9 expression. Further mechanistic studies revealed that DERCNC upregulated SOX9 by increasing the enrichment of H3K27ac modifications near the SOX9 promoter.
In conclusion, DERCNC expression in CHCC has significant clinical implications and can aggravate tumor proliferation by targeting SOX9. This represents a novel mechanism by which cirrhosis promotes tumor progression.
本研究旨在通过分析肝硬化肝细胞癌（CHCC）和非肝硬化肝细胞癌（NCHCC）之间长链非编码RNA（lncRNA）的差异表达，了解肝硬化在促进肝细胞癌（HCC）进展中的作用。
使用转录谱阵列鉴定差异表达的lncRNA。随后，选择一种特定的lncRNA，通过实验和实验评估其临床意义、潜在功能、调控靶点和途径。
该研究鉴定出一种lncRNA，我们将其命名为DERCNC，即肝硬化和非肝硬化HCC之间差异表达RNA的首字母缩写。DERCNC在CHCC中的表达明显高于NCHCC。临床上，DERCNC表达水平升高与肝硬化状态和肿瘤分期均呈正相关，与肿瘤分化呈负相关。此外，DERCNC的高表达与患者预后不良相关。发现肝星状细胞（LX2）的条件培养基可增强DERCNC表达、SOX9表达和肿瘤增殖。DERCNC的过表达同样促进肿瘤增殖并增加SOX9水平。相反，DERCNC沉默则产生相反的效果。此外，DERCNC的促增殖功能可通过调节SOX9表达而逆转。进一步的机制研究表明，DERCNC通过增加SOX9启动子附近H3K27ac修饰的富集来上调SOX9。
总之，CHCC中DERCNC的表达具有重要的临床意义，并且可以通过靶向SOX9加重肿瘤增殖。这代表了肝硬化促进肿瘤进展的一种新机制。
