THE ANTI-APOPTOTIC FUNCTION OF HNRNP K IN HEPATOCELLULAR CARCINOMA CELL LINES

Abstract

hnRNP K is upregulated in various cancers, including hepatocellular carcinoma (HCC), which is the third highest cause of cancer-related deaths globally, with apoptosis dysregulation as one of its hallmarks. hnRNP K has been implicated in apoptosis but its precise role in this process has not been clearly defined. Using 5-Fluorouracil to induce apoptosis in HCC cell lines, hnRNP K was found to be downregulated and this was also shown to be p53-independent. Downregulation of hnRNP K expression with siRNA significantly decreased cell viability and induced apoptosis. Investigation into the underlying mechanism with simultaneous downregulation of hnRNP K with caspase-8 or -9 intriguingly revealed that only caspase-8 siRNA abrogated hnRNPK-downregulation-induced apoptosis. Moreover, enhanced TRAIL potency independent of BID cleavage was also observed in hnRNP K siRNA-treated cells exposed to TRAIL. Exon array was performed on hnRNP K siRNA-treated Hep 3B and genes associated with caspase-8 function were selected for further analysis, revealing that BIRC3, CFLAR and XIAP correlated with hnRNP K expression. This study establishes that hnRNP K plays an anti-apoptotic role in HCC via the caspase-8 pathway and helps in identifying hnRNP K as a probable diagnostic and therapeutic marker.