Moreover, aflatoxin exposure, alcohol abuse, and metabolic disorders have also been recognized as major risk factors. 1 In most cases, HCC arises in cirrhotic livers, and the major cause is related to chronic liver injury caused by viral infections. Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide and is estimated to represent 50% of new cancer cases in China. sodium dodecyl sulfate polyacrylamide gel electrophoresis.glyceraldehyde 3-phosphate dehydrogenase.Akt/protein kinase B signaling inhibitor 2.Conclusion: We demonstrate that HULC promotes the phosphorylation of YB-1 through the extracellular signal–regulated kinase pathway, in turn regulates the interaction of YB-1 with certain oncogenic mRNAs, and consequently accelerates the translation of these mRNAs in the process of tumorigenesis. In addition, we found that HULC promotes the phosphorylation of YB-1 protein mainly through extracellular signal–regulated kinase. As a consequence, translation of silenced oncogenic mRNAs would be activated, including cyclin D1, cyclin E1, and matrix metalloproteinase 3. Our study further demonstrated that HULC could promote the phosphorylation of YB-1 protein, which leads to the release of YB-1 from its bound mRNA. YB-1 is a major component of translationally inactive messenger ribonucleoprotein particles which keeps mRNA in a silent state. Moreover, we show that HULC specifically binds to Y-box binding protein 1 (YB-1) protein both in vitro and in vivo. Meanwhile, HULC could promote cell proliferation, migration, and invasion in vitro and inhibit cisplatin-induced apoptosis. Furthermore, up-regulation of HULC was correlated with grading and overall survival. First, we validated the markedly increased expression levels of HULC in hepatocellular carcinoma tissues compared to their adjacent noncancerous tissues. Here, we demonstrate a novel mechanism by which long noncoding RNA plays oncogenic roles through modulating the phosphorylation status of its interaction protein. However, the detailed mechanisms of HULC remain unclear. The long noncoding RNA highly up-regulated in liver cancer (HULC) was first characterized in hepatocellular carcinoma. Dysregulated expression of long noncoding RNAs has been reported in many types of cancers, indicating that it may play a critical role in tumorigenesis.
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