Epigenetic-modification associated hnRNPA3 acts as a prognostic biomarker and promotes malignant progression of HCC.

OBJECTIVE

hnRNPA3 is highly expressed in numerous malignancies, including hepatocellular carcinoma (HCC), but its function and mechanism has not been elucidated. In this study, we performed a comprehensive bioinformatics analysis of hnRNPA3 in the TCGA-LIHC dataset and several experiments in vitro to investigate the function and potential mechanisms of hnRNPA3 in HCC.

METHODS

Pan-cancer expression including hnRNPA3 levels as well as DNA methylation, associated ceRNA, immune infiltration, and immune checkpoint genes of hnRNPA3 in TCGA-LIHC dataset were assessed. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling were used to evaluate prognostic values of hnRNPA3 in HCC. hnRNPA3 level in cell subtypes in HCC tumor microenvironment was analysed through spatial transcriptomic. "pRRophetic" package was used to predict potential chemotherapeutic drugs sensitivity. hnRNPA3 level in HCC patients and cell lines were detected by qRT-PCR or WB. hnRNPA3's impact on proliferation, migration were studied in SNU449 and HuH7 cell lines. RNA-seq showed hnRNPA3 controled different important singaling passways in HCC.

RESULTS

hnRNPA3 was significantly elevated in HCC tumors compared to controls. hnRNPA3 levels correlated with Age, HCC stage, histologic grade, and tumor status, and may independently predict the overall and disease-specific survival. Significant associations were found between hnRNPA3 levels and DNA methylation. hsa-miR-22-3p may act as a regulatory factor for hnRNPA3 and form a ceRNA network with multiple lncRNAs.Analysis of immune infiltration and immune checkpoint genes revealed a correlation between hnRNPA3 expression and macrophages. The similar conclusion also occurred in the spatial transcriptomic detection. 5-Fluorouracil, Doxorubicin, Etoposide, et al., may be potential sensitive drugs in therapy of high-hnRNPA3 HCC patients. Silencing hnRNPA3 expression in SNU449 and HuH7 cells resulted in reducing proliferation and migration. RNA-seq showed hnRNPA3 played an important regulatory role in the malignant progression of HCC.

CONCLUSION

hnRNPA3 was found to represent a promising biomarker within HCC diagnosis and prognosis and maybe a potential drug-target in HCC therapy.