Heterogeneous nuclear ribonucleoprotein A1 promotes the expression of autophagy-related protein 6 in human colorectal cancer.

Autophagy, a lysosomal self-degradative process of cellular components, is essential for cellular homeostasis to response cellular stress and is tightly controlled by autophagy-related genes (ATGs). Autophagy-related gene 6 (ATG6, also known as Beclin-1 in human) is an essential factor regulating autophagy and apoptosis. RNA binding proteins (RBPs) regulate gene expression at the post-transcriptional level and their differential expression is linked to the pathogenesis of several human diseases. Here, we demonstrate the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as a novel factor regulating ATG6 expression. hnRNPA1 associates with the 3' untranslated region (3'UTR) of ATG6 mRNA and promotes its expression without significant changes at the mRNA level. Knockdown of hnRNPA1 decreases ATG6 expression, which is enhanced by the overexpression of hnRNPA1. Also, we show augmented expression of both hnRNPA1 and ATG6 in the colorectal cancer (CRC) tissues obtained from patients and demonstrate a positive correlation of their expression in CRC tissues. Our results suggest the potential role of hnRNPA1-mediated ATG6 regulation in the pathogenesis of CRC.