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Positive Feedback Regulation of Glycolysis by H4K5 Lactylation Promotes Malignant Progression of Hepatocellular Carcinoma [RNA-seq]

GSE314771 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/04/22 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Hepatocellular carcinomaThis series is part of our curated briefing on it.
Samples
12 samples: 6 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
H4K5 lactylation - ENO2 loop drives glycolysis and HCC progressionJHEP reports : innovation in hepatology · 2026
Summary (written by the submitters)
[Background & Aims] Histone lactylation is a lactate-dependent epigenetic modification driven by glycolysis. Although elevated histone lactylation has been reported in various cancer, the biological relevance of histone H4 lactylation in HCC remains unclear. This study aimed to investigate the clinicopathological relevance of H4K5 lactylation (H4K5la) and its role in regulating lactate metabolism to promote HCC progression.
Read the full summary ↓
[Methods] The expression levels of H4K5la, H3K18la, and PanKla were evaluated in HCC tissues by immunohistochemistry. RNA-seq and ChIP-PCR analyses were performed on HCC cells treated with lactate to identify the downstream target genes mediated by H4K5la. Functional validation of these targets was conducted through knockdown and overexpression experiments, and biological effects were assessed both in vitro and in vivo. [Results] Elevated levels of H4K5la, H3K18la, and PanKla were associated with a poor prognosis, with H4K5la identified as an independent prognostic factor of overall survival. Upon lactate treatment, five genes including glycolytic enzyme ENO2 were consistently identified in three HCC cell lines, showing enrichment of H4K5la at their promoter regions. ENO2-KD reduced intracellular lactate and H4K5la levels, as well as in vivo tumorigenicity in HCC cells, while ENO2 overexpression exerted opposite functions. These findings establish a positive feedback loop: H4K5la increases ENO2 expression, which in turn amplifies glycolysis and lactate production, further elevating H4K5la. Moreover, ENO2 expression was tightly correlated with H4K5la levels in HCC tissues. [Conclusions] High H4K5la expression is an independent prognostic biomarker in HCC. H4K5la promotes HCC aggressiveness by enhancing glycolysis and tumor growth, forming a positive feedback loop with ENO2. Targeting this pathway may represent a promising therapeutic strategy for HCC.
Published in
H4K5 lactylation - ENO2 loop drives glycolysis and HCC progression
Yamane M, Akiyama Y, Shimada S et al. · JHEP reports : innovation in hepatology 2026 · PMID 41962496 · doi:10.1016/j.jhepr.2026.101786
This dataset
Open GSE314771 in finder → Find more human RNA-seq datasets → Hepatocellular carcinoma landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE314771_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1392575 and SRA study SRP657401. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41962496) ↗
Study design
6 conditions, mostly in duplicate
HLF_NM ×2 HLF_LAC ×2 SNU475_NM ×2 SNU475_LAC ×2 PLC/PRF/5_NM ×2 PLC/PRF/5_LAC ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Hepatocellular carcinoma datasets

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