@Article{or.2025.068737,
AUTHOR = {Huihui Shi, Lei Chen, Juan Huang, Xuejing Lin, Lei Huang, Min Tang, Kai Lu, Wenchao Wang, Maoling Zhu},
TITLE = {<i>CSRNP1</i> Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in Hepatocellular Carcinoma},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {1},
PAGES = {0--0},
URL = {http://www.techscience.com/or/v34n1/65173},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms, with a particular focus on mitochondrial function and apoptosis. <b>Methods:</b> Differential expression analyses were performed across three datasets—The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), GSE36076, and GSE95698—to identify overlapping differentially expressed genes (DEGs). A prognostic risk model was then constructed. Cysteine/serine-rich nuclear protein 1 (<i>CSRNP1</i>) expression levels in HCC cell lines were assessed via western blot (WB) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of <i>CSRNP1</i> knockdown or overexpression on cell proliferation, migration, and apoptosis were evaluated using cell counting-8 (CCK-8) assays, Transwell assays, and flow cytometry. Mitochondrial ultrastructure was examined by transmission electron microscopy, and intracellular and mitochondrial reactive oxygen species (mROS) levels were measured using specific fluorescent probes. WB was used to assess activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) pathway, and pathway dependence was examined using the ROS scavenger N-Acetylcysteine (NAC) and the JNK inhibitor SP600125. <b>Results:</b> A six-gene prognostic model was established, comprising downregulated genes (<i>NR4A1</i> and <i>CSRNP1</i>) and upregulated genes (<i>CENPQ</i>, <i>YAE1</i>, <i>FANCF</i>, and <i>POC5</i>) in HCC. Functional experiments revealed that <i>CSRNP1</i> knockdown promoted the proliferation of HCC cells and suppressed their apoptosis. Conversely, <i>CSRNP1</i> overexpression impaired mitochondrial integrity, increased both mitochondrial and cytoplasmic ROS levels, and activated the JNK/p38 MAPK pathway. Notably, treatment with NAC or SP600125 attenuated <i>CSRNP1</i>-induced MAPK activation and apoptosis. <b>Conclusion:</b> <i>CSRNP1</i> is a novel prognostic biomarker and tumor suppressor in HCC. It exerts anti-tumor effects by inducing oxidative stress and activating the JNK/p38 MAPK pathway in a ROS-dependent manner. These findings suggest that <i>CSRNP1</i> may serve as a potential therapeutic target in the management of HCC.},
DOI = {10.32604/or.2025.068737}
}