Mechanistic insights into ENO2-driven glycolysis and tumor progression in hepatocellular carcinoma
5 affiliations
- 1Guizhou Provincial People’s Hospital, Department of Hepatobiliary Surgery, Guiyang, Guizhou Province, China
- 2Guizhou Medical University, School of Basic Medical Sciences, Anshun, Guizhou Province, China
- 3Department of Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
- 4Department of Surgery, The First People’s Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
- 5Guiyang Nanming District People’s Hospital, Department of Surgery, Guizhou Province, China
Abstract
Background and Aims: Neuron-specific enolase 2 (ENO2) has been implicated in tumor metabolism, but its biological role in hepatocellular carcinoma remains incompletely defined. This study aimed to investigate the expression, prognostic relevance, and functional role of ENO2 in HCC. Methods: Public transcriptomic datasets, RNA sequencing, WGCNA, survival analyses, and pathway enrichment analyses were integrated to identify HCC-associated genes. ENO2 expression was validated in HCC cell lines and paired clinical tissues.Gain- and loss-of-function, catalytic-rescue, glycolytic-inhibition, and pyruvate-rescue experiments were performed to evaluate glycolytic activity, proliferation, colony formation, migration, invasion, and tumor growth. Results: ENO2 was upregulated in HCC and was associated with advanced tumor stage and unfavorable survival outcomes in public datasets. ENO2 overexpression increased glycolytic activity and malignant phenotypes, whereas ENO2 depletion produced opposite effects. In ENO2-depleted cells, re-expression of shRNA-resistant ENO2 wild type restored the impaired glycolytic and malignant phenotypes, whereas the catalytic-deficient ENO2 mutant failed to restore them. Moreover, 2-deoxy-D-glucose attenuated ENO2 overexpression-associated phenotypes, while pyruvate partially rescued phenotypes associated with ENO2 depletion. ENO2 expression was also associated with altered PI3K and AKT phosphorylation. Conclusions: ENO2 may contribute to HCC progression by enhancing glycolytic metabolism and malignant phenotypes, partly in association with PI3K/AKT signaling. ENO2 is a candidate metabolic and prognostic biomarker that requires validation in larger independent clinical cohorts and warrants further investigation as a therapeutic candidate.
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BibTeX
@article{liu2026mechanistic,
title = {{Mechanistic insights into ENO2-driven glycolysis and tumor progression in hepatocellular carcinoma}},
author = {Yan Liu and Xiao-Ran Zhang and Li Dai and Hai-Liang Li and Xiang-Ren Jin and Hong-Bin Qi and Ke Tang and Qiang Li},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0361057},
url = {https://doi.org/10.1371/journal.pone.0361057},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanistic insights into ENO2-driven glycolysis and tumor progression in hepatocellular carcinoma
AU - Yan Liu
AU - Xiao-Ran Zhang
AU - Li Dai
AU - Hai-Liang Li
AU - Xiang-Ren Jin
AU - Hong-Bin Qi
AU - Ke Tang
AU - Qiang Li
PY - 2026
DA - 2026/10/27
JO - PLOS One
DO - 10.1371/journal.pone.0361057
UR - https://doi.org/10.1371/journal.pone.0361057
AB - Background and Aims: Neuron-specific enolase 2 (ENO2) has been implicated in tumor metabolism, but its biological role in hepatocellular carcinoma remains incompletely defined. This study aimed to investigate the expression, prognostic relevance, and functional role of ENO2 in HCC. Methods: Public transcriptomic datasets, RNA sequencing, WGCNA, survival analyses, and pathway enrichment analyses were integrated to identify HCC-associated genes. ENO2 expression was validated in HCC cell lines and paired clinical tissues.Gain- and loss-of-function, catalytic-rescue, glycolytic-inhibition, and pyruvate-rescue experiments were performed to evaluate glycolytic activity, proliferation, colony formation, migration, invasion, and tumor growth. Results: ENO2 was upregulated in HCC and was associated with advanced tumor stage and unfavorable survival outcomes in public datasets. ENO2 overexpression increased glycolytic activity and malignant phenotypes, whereas ENO2 depletion produced opposite effects. In ENO2-depleted cells, re-expression of shRNA-resistant ENO2 wild type restored the impaired glycolytic and malignant phenotypes, whereas the catalytic-deficient ENO2 mutant failed to restore them. Moreover, 2-deoxy-D-glucose attenuated ENO2 overexpression-associated phenotypes, while pyruvate partially rescued phenotypes associated with ENO2 depletion. ENO2 expression was also associated with altered PI3K and AKT phosphorylation. Conclusions: ENO2 may contribute to HCC progression by enhancing glycolytic metabolism and malignant phenotypes, partly in association with PI3K/AKT signaling. ENO2 is a candidate metabolic and prognostic biomarker that requires validation in larger independent clinical cohorts and warrants further investigation as a therapeutic candidate.
SN - 1932-6203
ER -