The following is a summary of “Epigenetic-modification associated hnRNPA3 acts as a prognostic biomarker and promotes malignant progression of HCC,” published in the April 2025 issue of BMC Cancer by Cai et al.

Heterogeneous nuclear ribonucleoprotein A3 (hnRNPA3) has been implicated in several malignancies, including hepatocellular carcinoma (HCC), yet its specific biological role and underlying molecular mechanisms in HCC remain poorly characterized. This study integrates a comprehensive bioinformatics analysis with functional in vitro assays to elucidate the expression patterns, prognostic relevance, immune associations, and mechanistic impact of hnRNPA3 in the progression of HCC.

Researchers analyzed pan-cancer expression datasets, with a focus on TCGA-LIHC cohort, to assess hnRNPA3 expression, DNA methylation status, competing endogenous RNA (ceRNA) interactions, immune infiltration, and associations with immune checkpoint markers. Prognostic significance was evaluated using logistic regression, receiver operating characteristic analysis, Kaplan–Meier survival curves, and nomogram models. Spatial transcriptomics was employed to identify hnRNPA3 expression across cell subtypes within the HCC tumor microenvironment. The “pRRophetic” R package was utilized to predict chemotherapeutic drug sensitivity based on hnRNPA3 expression levels. Quantitative reverse transcription PCR (qRT-PCR) and Western blotting (WB) were used to detect hnRNPA3 expression in patient samples and HCC cell lines. Functional assays in SNU449 and HuH7 cells examined the effects of hnRNPA3 silencing on proliferation and migration. RNA sequencing (RNA-seq) was performed to identify pathways regulated by hnRNPA3.

hnRNPA3 was significantly overexpressed in HCC tissues compared to normal liver tissues. Elevated hnRNPA3 expression correlated with advanced tumor stage, higher histological grade, patient age, and active tumor status. Survival analyses suggested hnRNPA3 as an independent predictor of both overall survival and disease-specific survival. Differential methylation was observed in hnRNPA3, suggesting epigenetic regulation. The miRNA hsa-miR-22-3p was identified as a potential regulator of hnRNPA3, forming a ceRNA network with various lncRNAs. Immune infiltration analysis showed a strong association between hnRNPA3 expression and macrophage abundance, supported by spatial transcriptomic data. Predictive modeling indicated that high hnRNPA3 expression may sensitize tumors to agents such as 5-fluorouracil, doxorubicin, and etoposide. Functional experiments demonstrated that hnRNPA3 knockdown significantly reduced cell proliferation and migration. Transcriptomic profiling further revealed that hnRNPA3 regulates key oncogenic pathways involved in HCC progression.

This study identifies hnRNPA3 as a critical oncogenic factor in hepatocellular carcinoma, with significant implications for diagnosis, prognosis, and treatment. Its overexpression is associated with tumor aggressiveness, immune microenvironment modulation, and chemotherapeutic sensitivity. hnRNPA3 holds potential as both a prognostic biomarker and a therapeutic target in HCC management.

Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14028-9