Role of RAGE-MKK4/MKK7-JNK1 pathway in type 2 diabetic patients with hepatocellular carcinoma.

MENG Li-heng; HUANG Yao; LI Shi-chun; QIN Ying-fen

doi:10.3969/j.issn.1001-9448.2017.10.011

Abstract：Objective To investigate the role of RAGE, MKK4, MKK7 and JNK1 in type 2 diabetic mellitus patients with hepatocellular carcinoma (HCC).Methods The carcinoma tissues and their adjacent tissues in 18 cases of type 2 diabetic mellitus patients with HCC (Group DMHC) and 30 cases of HCC (Group HCC) were collected.The expression of RAGE, MKK4, MKK7 and JNK1 was assessed with Western Blotting.Results The RAGE, MKK7 and JNK1 protein levels were significantly higher in cancer tissues in both Group HCC and DMHC than their corresponding adjacent tissues, while MKK4 expression was significantly lower (all P<0.05).Compared with the Group HCC, MKK7 and JNK1 expression in cancer tissues of Group DMHC was significantly enhanced (all P<0.05).In Group HCC and DMHC, the expression of MKK7 and JNK1 was significantly increased in poorly differentiated cancer tissues as compared with highly differentiated cancer tissues (all P<0.01).Moreover, JNK1 and MKK7 expression was significantly elevated in poorly differentiated cancer tissues of the Group DMHC compared to those of Group HCC (all P<0.05).In Group HCC, the expression of RAGE was significantly increased in poorly differentiated cancer tissues as compared to highly differentiated cancer tissues (P<0.05).In Group DMHC, the expression MKK4 in cancer tissues of patients with cancer metastasis was significantly reduced (P<0.05).The level of RAGE was both significantly positively correlated with MKK7 and JNK1 in cancer tissues of Group HCC and DMHC (both P<0.05).Conclusion The increase of RAGE expression may be involved in the occurrence and development of HCC.MKK4 reduction may be one of risk factors of HCC and DMHC.The expression of MKK7 and JNK1 might promote the progression of HCC in T2DM patients.MKK4 in DMHC cancer tissues may have the role of inhibition of tumor metastasis.MKK7 and JNK1 may be regulated by RAGE at a certain level.