Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling

Sep 21, 2026

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Research investigates how the achaete-scute family bHLH transcription factor 1 (ASCL1) regulates solute carrier family 6 member 13 (SLC6A13) to affect hepatocellular carcinoma (HCC) progression through glycine-inflammasome signaling. Differential expression analyses used TCGA-LIHC plus GSE14520 and GSE67764 datasets, followed by Kaplan–Meier survival assessment of SLC6A13 prognostic value. JASPAR and dual-luciferase assays tested transcriptional regulation, while cell experiments examined ASCL1/SLC6A13 overexpression, ethanol effects, and glycine modulation on inflammatory cytokines and inflammasome activation. Results link reduced SLC6A13 with better prognosis and show ASCL1/SLC6A13 suppress malignant behaviors yet enhance inflammasome activation, which ethanol amplifies and glycine attenuates.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Introduction

Inflammation and aging in HCC

Research approach and targets

Differential gene expression and survival analysis

Transcriptional regulation and functional assays

RESEARCH ARTICLE Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling Hongyan Zhang 1 ∗ \#, Ruiqing Zong 1\#, Huiqi Wu 1, Jun Jiang 2, Chuanyong Liu 3 ∗, and Suiyi Liu 4 ∗ Hepatocellular carcinoma (HCC), the most common primary liver cancer, typically arises from chronic liver conditions such as hepatitis, cirrhosis, or other chronic liver diseases, and is characterized by its aggressive nature and poor prognosis. The purpose of this research was to clarify the function of achaete-scute family bHLH transcription factor 1 (ASCL1) and solute carrier family 6 member 13 (SLC6A13) in influencing tumor cell behavior, inflammatory responses, and the regulation of inflammasomes. We analyzed the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database, as well as in the GSE14520 and GSE67764 datasets, to identify the expression changes ofSLC6A13 in liver cancer. The prognostic significance ofSLC6A13 in LIHC was assessed through Kaplan-Meier survival curve analysis. Transcriptional regulation ofSLC6A13 by ASCL1 was explored using the Joint Annotation of the Human Genome and other species by the Systematic Pipeline for the Annotation of Regulatory Regions (JASPAR) database and dual-luciferase assays. In vitro experiments investigated the impact of ASCL1 and SLC6A13 overexpression on HCC cell growth. Additionally, the effects of ethanol treatment and glycine modulation on the inflammatory response in HCC cell lines were evaluated. HCC samples showed reduced levels ofSLC6A13, which correlates with a better prognosis for liver metastases. Elevated SLC6A13 expression correlated with improved overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS). ASCL1 upregulated SLC6A13 and inhibited proliferation, migration, and invasion of HCC cells. Ethanol induced the production of inflammatory cytokines, which was enhanced by overexpression ofSLC6A13 but counteracted by glycine. This study highlighted elevated expression ofSLC6A13 in LIHC which has been correlated with improved OS, PFS, RFS, and DSS. Overexpression ofSLC6A13 and ASCL1 in HCC cells enhanced inflammasome activation, which was exacerbated by ethanol and attenuated by glycine. Keywords: Solute carrier family 6 member 13 (SLC6A13), hepatocellular carcinoma (HCC), transcription factor, achaete-scute family bHLH transcription factor 1 (ASCL1), glycine-inflammasome signaling. Introduction Around 95% of primary liver malignancies are attributed to hepatocellular carcinoma (HCC), the most prevalent primary liver malignancy [1, 2] . The onset of liver cancer is insidious and has no obvious speciﬁcity in the early stage [3] . As the disease progresses, patients may experience pain, abdominal swelling, fatigue, and a mass in the upper abdomen [4, 5] . Other symptoms that can occur in patients with liver cancer include low-grade fever, jaundice, diarrhea, and upper gastrointestinal bleeding [6, 7] . According to research, liver cancer can induce a variety of diﬀerent disorders, such as hepatic encephalopathy, liver failure, metastatic liver cancer, and so on [8, 9] . Currently, risk factors include hepatitis B and C viruses, among others [10, 11] . Since the etiology of HCC is intricate and varied, there is now no eﬀective treatment, even though several research studies are carried out annually on the care of HCC patients. Targeted medicines have been approved as a result of recent developments in the molecular pathophysiology of HCC, which have also helped identify possible therapeutic targets. Therefore, the search for reliable biomarkers for early detection, prognosis, and treatment response is a key area of ongoing research. Inﬂammation, characterized by an increase in low-grade chronic inﬂammation with age, serves as a hallmark of aging and is closely associated with v

FAQs

What roles do ASCL1 and SLC6A13 play in hepatocellular carcinoma progression?

ASCL1 upregulates SLC6A13 and inhibits HCC cell proliferation, migration, and invasion. The study also links ASCL1/SLC6A13 to changes in inflammatory signaling and inflammasome activation.

How was SLC6A13 evaluated for its clinical significance in LIHC?

SLC6A13 expression changes were assessed using TCGA-LIHC and external datasets (GSE14520, GSE67764), and prognostic significance was tested with Kaplan–Meier survival analyses.

How do ethanol and glycine influence inflammation and inflammasome activation in HCC cells?

Ethanol induces inflammatory cytokines, which are enhanced by SLC6A13 overexpression but counteracted by glycine. Inflammasome activation is exacerbated by ethanol and attenuated by glycine.

Sep 21, 2026

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