NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway

Sep 21, 2026

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Nucleolar protein 16 (NOP16) is regulated by c-Myc and shows dysregulation across multiple cancers. This study analyzes NOP16 expression in hepatocellular carcinoma (LIHC) using TCGA and GEO datasets, survival modeling, ROC-based evaluation, KEGG and GSEA enrichment, and complementary in vitro assays including siRNA knockdown. Knockdown activates Keap/Nrf2 signaling and suppresses invasion, migration, and EMT progression, while LIHC single-cell sequencing links NOP16 mainly to T lymphocytes. High NOP16 predicts adverse prognosis and marks LIHC progression.

LanguageEnglish

CategoryHealthcare

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Pages21

Reading Time53 min

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Introduction

Rationale and clinical need for biomarkers in hepatocellular carcinoma

NOP16 function and unresolved mechanism

Oxidative stress and the Keap1-Nrf2 signaling pathway

Technology and Health Care 32 (2024) 2463–2483 2463 DOI 10.3233/THC-231256 IOS Press NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway Shangdong Mua , Qiusi Tianb and Liangyu Shenc ;􀀃 a Department of Oncology, Health Science Center, 3201 Hospital of Xi'an Jiaotong University, Hanzhong, Shaanxi, China b Department of Neurosurgery, Health Science Center, 3201 Hospital of Xi'an Jiaotong University, Hanzhong, Shaanxi, China c Department of Anesthesia, Operation Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China Received 10 September 2023 Accepted 29 November 2023 Abstract. BACKGROUND: Nucleolar protein 16 (NOP16) is present in the protein complex of the nucleolus. The NOP16 promoter contains a c-Myc binding site, and the transcriptional regulation by c-Myc directly regulates NOP16 expression levels. OBJECTIVE: Dysregulation of NOP 16 is currently reported in only a small number of cancers. In this study, the expression proﬁle of NOP 16 in hepatocellular carcinoma (LIHC) and its clinical signiﬁcance were analyzed. METHODS: NOP16 expression in hepatocellular carcinoma (LIHC) and its relationship with the clinical characters of LIHC were examined using the Cancer Genome Atlas (TCGA), the Gene Expression comprehensive database (GEO), KaplanMeier survival analysis, univariate Cox analysis, multivariate Cox analysis, ROC curve analysis of KEGG enrichment, GSEA enrichment, in vitro experiments (e.g., siRNA interference of NOP16 expression in hepatoma cells, Keap1-Nrf2 pathway, cell cycle, cell apoptosis and Transwell assays), and LIHC single-cell sequencing (scRNA) . RESULTS: Pan-cancer analysis revealed that NOP16 was highly expressed in 20 cancer types, including LIHC, and high NOP16 expression was an independent adverse prognostic factor in LIHC patients. The expression levels of NOP16 mRNA and protein were signiﬁcantly increased in tumour tissues of LIHC patients compared to normal tissues. The functions of co-expressed genes were primarily enriched in the cell cycle and reactive oxygen species metabolism. The experimental results showed that knockdown of NOP16 activated the Keap/Nrf2 signalling pathway and inhibited the invasion, migration, and EMT progression of LIHC cells. LIHC scRNA-seq data showed that NOP16 was primarily expressed in T lymphocytes. CONCLUSIONS: NOP16 promoted cancer development in LIHC and caused an imbalance in Keap/Nrf2 signalling, which subsequently caused the aberrant expression of genes typical for EMT, cell cycle progression and apoptosis. NOP16 is a potential prognostic marker and therapeutic target for hepatocellular carcinoma progression. Keywords: NOP16, Keap1-Nrf2 pathway, hepatic cell liver cancer, bioinformatics 􀀃 Corresponding author: Liangyu Shen, Department of Anesthesia, Operation Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. E-mail: [Sasdf08150809@163.com](Sasdf08150809@163.com). 0928-7329 􀀍c 2024 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4 .0) . 2464 S. Mu et al. / NOP16 promotes hepatocellular carcinoma progression and triggers EMT through 1. Introduction Primary liver cancer is one of the most common malignant tumours in humans and the third leading cause of cancer death worldwide (8.3%) . It is primarily divided into three mixed types, LIHC, cholangiocytic carcinoma (ICC) and LIHC-ICC, which account for approximately 90% of all liver cancer cases [1] . There is no obvious speciﬁc shape of LIHC in the early stage, and greater than 50% of patients have reached the middle and late stages at the time of diagnosis. Due to the inﬂuence of postoperative recurrence and cancer metastasi

FAQs

What is the main role of NOP16 in hepatocellular carcinoma (LIHC)?

NOP16 is highly expressed in LIHC and acts as an independent adverse prognostic factor. It promotes cancer progression by affecting pathways linked to EMT and cell-cycle regulation.

How does NOP16 influence EMT and invasion in LIHC cells?

Experimental knockdown of NOP16 inhibits invasion, migration, and EMT progression. This effect is associated with activation of the Keap/Nrf2 signaling pathway.

Which signaling pathway connects NOP16 to EMT-related gene dysregulation?

The study links NOP16-driven progression to an imbalance in Keap1-Nrf2 signaling. This imbalance leads to aberrant expression of EMT-typical genes, along with cell-cycle progression and apoptosis-related changes.

Sep 21, 2026

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