Investigating the Expression and Function of PPP2R1A in Hepatocellular Carcinoma: A Multi-Omics Analysis with in vitro Validation.
- 1Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People's Republic of China.
- 2Graduate School, Guangxi University of Chinese Medicine, Nanning, 530200, People's Republic of China.
- 3Key Laboratory of Chinese Medicine Clinical Research, Education Department of Guangxi Zhuang Autonomous Region, Nanning, 530023, People's Republic of China.
Abstract
Hepatocellular carcinoma (HCC) remains difficult to diagnose early and to treat effectively. Protein Phosphatase 2A Regulatory Subunit Aα (PPP2R1A), the scaffolding (Aα) subunit of the PP2A holoenzyme, is altered in several cancer types, but its expression pattern, functional significance, and translational relevance in HCC are incompletely understood. Public transcriptomic, single-cell, and spatial transcriptomic datasets (TCGA-LIHC, GTEx, GEO, ICGC-LIHC, HPA, TISCH2) and drug-sensitivity databases were integrated to characterize PPP2R1A expression and its associations with survival, biological pathways, and tumor immune infiltration in HCC. Functional effects of PPP2R1A knockdown were assessed in Huh7 cells by RT-qPCR, CCK-8, Transwell, flow-cytometric cell-cycle, and β-galactosidase assays. PPP2R1A was significantly overexpressed in HCC tissues relative to normal liver and was also elevated across several other cancer types. High PPP2R1A expression was associated with shorter overall and disease-specific survival in Kaplan-Meier analysis, although it was not an independent prognostic factor after multivariate adjustment (hazard ratio [HR] = 1.051, p = 0.789). PPP2R1A expression correlated positively with transcriptional programs related to cell cycle, MYC, EGFR, MAPK, and WNT signaling, and negatively with p53 pathway activity. At single-cell and spatial resolution, PPP2R1A was enriched in malignant cells and in tumor regions, and its expression correlated with the abundance of several computationally inferred immune cell populations. PPP2R1A knockdown in Huh7 cells reduced proliferation and invasion, induced G2-phase arrest, and decreased MYC, CDK1, and CCNB1 mRNA expression without inducing senescence. Drug-sensitivity screens suggested candidate agents, such as AT-7519, that warrant further investigation in PPP2R1A-high HCC. PPP2R1A is consistently overexpressed in HCC and contributes to the malignant phenotype at least partly through cell-cycle regulation. These findings are hypothesis-generating, and the potential diagnostic, prognostic, or therapeutic value of PPP2R1A in HCC requires dedicated prospective and functional validation.
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BibTeX
@article{tan2026investigating,
title = {{Investigating the Expression and Function of PPP2R1A in Hepatocellular Carcinoma: A Multi-Omics Analysis with in vitro Validation.}},
author = {Jinna Tan and Yangling Zeng and Hemeng Wu and Yuni Liang and Yunshan Qiu and Qiulian Mo and Yuzhen Luo and Jiaqian He and Yunyong Wang and Hui Yin and Peipei Chen and Mingfen Li and Hongsheng Lin},
journal = {Journal of hepatocellular carcinoma},
year = {2026},
month = nov,
doi = {10.2147/jhc.s641006},
url = {https://europepmc.org/article/MED/42999840},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Investigating the Expression and Function of PPP2R1A in Hepatocellular Carcinoma: A Multi-Omics Analysis with in vitro Validation.
AU - Jinna Tan
AU - Yangling Zeng
AU - Hemeng Wu
AU - Yuni Liang
AU - Yunshan Qiu
AU - Qiulian Mo
AU - Yuzhen Luo
AU - Jiaqian He
AU - Yunyong Wang
AU - Hui Yin
AU - Peipei Chen
AU - Mingfen Li
AU - Hongsheng Lin
PY - 2026
DA - 2026/11/03
JO - Journal of hepatocellular carcinoma
DO - 10.2147/jhc.s641006
UR - https://europepmc.org/article/MED/42999840
AB - Hepatocellular carcinoma (HCC) remains difficult to diagnose early and to treat effectively. Protein Phosphatase 2A Regulatory Subunit Aα (PPP2R1A), the scaffolding (Aα) subunit of the PP2A holoenzyme, is altered in several cancer types, but its expression pattern, functional significance, and translational relevance in HCC are incompletely understood. Public transcriptomic, single-cell, and spatial transcriptomic datasets (TCGA-LIHC, GTEx, GEO, ICGC-LIHC, HPA, TISCH2) and drug-sensitivity databases were integrated to characterize PPP2R1A expression and its associations with survival, biological pathways, and tumor immune infiltration in HCC. Functional effects of PPP2R1A knockdown were assessed in Huh7 cells by RT-qPCR, CCK-8, Transwell, flow-cytometric cell-cycle, and β-galactosidase assays. PPP2R1A was significantly overexpressed in HCC tissues relative to normal liver and was also elevated across several other cancer types. High PPP2R1A expression was associated with shorter overall and disease-specific survival in Kaplan-Meier analysis, although it was not an independent prognostic factor after multivariate adjustment (hazard ratio [HR] = 1.051, p = 0.789). PPP2R1A expression correlated positively with transcriptional programs related to cell cycle, MYC, EGFR, MAPK, and WNT signaling, and negatively with p53 pathway activity. At single-cell and spatial resolution, PPP2R1A was enriched in malignant cells and in tumor regions, and its expression correlated with the abundance of several computationally inferred immune cell populations. PPP2R1A knockdown in Huh7 cells reduced proliferation and invasion, induced G2-phase arrest, and decreased MYC, CDK1, and CCNB1 mRNA expression without inducing senescence. Drug-sensitivity screens suggested candidate agents, such as AT-7519, that warrant further investigation in PPP2R1A-high HCC. PPP2R1A is consistently overexpressed in HCC and contributes to the malignant phenotype at least partly through cell-cycle regulation. These findings are hypothesis-generating, and the potential diagnostic, prognostic, or therapeutic value of PPP2R1A in HCC requires dedicated prospective and functional validation.
SN - 2253-5969
ER -