Using pharmacologic and siRNA approaches, we show that the autocrine or paracrine activation of the EGF receptor (EGFR)/mitogen-activated protein/extracellular signal-regulated kinase pathway increases the IR-A:IR-B ratio in HCC cell lines, but not in normal hepatocytes, by upregulating the expression of the splicing factors CUGBP1, hnRNPH, hnRNPA1, hnRNPA2B1, and SF2/ASF.
Moreover small interfering RNA against hnRNP A2/B1 suppressed telomerase activity, and immunohistochemical examination showed that the enhanced nuclear and cytoplasmic hnRNP A2/B1 expression in HCC was significantly associated with histological grade of tumor differentiation and microvascular invasion of HCC.
We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues.