The Roles Of PKM2in The Malignant Progression Of Hepatocellular Carcinoma And Its Clinical Significance

Aim To explore the dynamic change of PKM2in process of hepatocarcinogenesis,analyze the expression of PKM2correlation with clinicopathologic features and prognosis,and reveal biological function of PKM2and its clinical signifance in HepatocellularCarcinoma.Materials and methods Hepatocellular carcinomas were induced with the adminstrationof diethylnitrosamine(DENA) in rats, Observe histological changes and PKM2dynamicexpression of the rat liver in the carcinogenesis process.345HCC cases with follow upinformation were examined by immunohistochemically staining to investigate theexpression of PKM2, p53and ki-67proteins. The relationship between the proteinsexpression and clinicopathologic characteristics of HCC were evaluated, and the potentialprognostic value of PKM2was also be investigated. Meanwhile, dual-luciferase reportergene was used to investigate relationship of regulation between microRNA-199a-3p andPKM2, further studies of their biological function and the role of HepG2to cisplatin drugsensitivityResults1.Immunohistochemisty results demonstrated the translocation of PKM2fromcytoplasma to nucleus with the progress of HCC induced by Diethylnitrosamine in rats.2.The expression (both in nuclei and cytoplasme)of PKM2in carcinoma wassignificantly higher than that in pericarcinomatous liver tissues. Increased expression ofPKM2was significantly correlated with increasing histologic grade, TNM stage, vascularcancer embolus, capsule status, preoperative lymph nodel and intrahepatic metastasis, AFPlevel, expression of Ki67and P53. Nuclear translocation of PKM2also correlated withtumor size and degree of fatty degeneration. On Kaplan-Meier regression analysis, highexpression of PKM2was found to have extremely poor prognosis. 3. PKM2protein expression was higher in HCC than pericarcinomatous liver tissuesin17/20cases, miRNA-199a-3p was lower in HCC than pericarcinomatous liver tissues in20/20cases.4. PKM2is the target gene of miRNA-199a-3p. Using dual luciferase reporter assaywe demonstrated that miRNA-199a-3p could interact with the3′UTR of PKM2directly.Moreover, the overexpression of miRNA-199a-3p could inhibit the high expression ofPKM2protein in HepG2cells.5. miRNA-199a-3p directed regulated PKM2, and involved in proliferation, invasion,and metastasis of hepatocellular carcinoma.6．PKM2involved in regulation of cell cycle, arrested cell cycle in G0-G1phase.7. miRNA-199a-3p and si-PKM2could enhance the sensitivity of HCC cells tocisplatin.Conclusions1. PKM2has the malignant transformational ability on hepatocyte, andclosely related with proliferation, invasion and metastasis of HCC.2. PKM2translocationof nuclei is a late event in process of hepatocarcinogenesis, And associate with aggressiveof HCC have prognostic significance.3. PKM2is a potential diagnostic, therapeutic andprognostic targets of HCC.