Targeting HNRNPA2B1 to overcome chemotherapy resistance in gastric cancer stem cells: Mechanisms and therapeutic potential.

Gastric cancer (GC) remains a significant global health challenge, particularly due to the resistance of gastric cancer stem cells (GCSCs) to chemotherapy. This study investigates the role of heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), a member of the heterogeneous nuclear ribonucleoproteins (hnRNPs), in modulating mitochondrial metabolic reprogramming and contributing to chemoresistance in GCSCs. Through extensive analysis of tumor cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets, HNRNPA2B1 was identified as a key regulator in GCSCs, correlating with poor prognosis and enhanced resistance to chemoresistance. CRISPR-Cas9 mediated knockout of HNRNPA2B1 in GCSCs led to a significant decrease in mitochondrial function, reduced migration, invasion, and sphere formation abilities, and markedly increased apoptosis. These changes were accompanied by a shift in metabolic activity, evidenced by decreased oxygen consumption and increased extracellular acidification. Our results highlight HNRNPA2B1 as a pivotal factor in sustaining the malignant phenotype of GCSCs and present it as a potential therapeutic target to improve chemotherapy efficacy in GC.