Midkine Trsndlocated To Nucleolus And Involved In RRNA Transcription And Anti-apoptosis

MK is a heparin-binding growth protein with a molecular weight of 13 kDa. It is strongly expressed during midgestation embryogenesis. Moreover, it can be detected in most carcinoma specimens at a high level in a tissue type-independent manner, including ones of esophageal, gastric, gall bladder, pancreas, colorectal, breast, and lung carcinomas, and Wilms' tumors, while it restricted in normal adult tissues. MK expression also increases with advancing stages of human carcinomas. Also, it can be detected in blood and unraniy of paitients with tumors. So, it is significantly linked to the prognosis.The data are inconsistent regarding the intracellular localization of MK. Previous studies showed that MK localizes in the nucleus, nucleolus, or cytosol. In this study, we found MK can translocate and accumulate into the nucleolus of HepG2 cells through tracking molecule GFP. We therefore further employed immunogold-labeling electron microscopy to investigate the exactly location of MK. The results showed that MK mainly localized in the GC, DFC and the border between the DFC and FC. Because nucleolus is a region for ribosomal biogenesis, it prompted us to hypothesize that MK may be involved in RNA transcription and processing. We subquently studied the effect of MK on rRNA synthesis, and found the transcription of 45S rRNA could be down-regulated by knock down of the MK. Furthermore, we found that MK acts anti-apoptosis when pretreatment with it in an apoptosis system. One of the hallmarks of cancer is sustained cell growth and this can only be achieved by increased protein synthesis. To accommodate this need, there must be an increase in ribosome biogenesis. The role MK plays in rRNA transcription in cancer cells suggests that up-regulation of MK expression in various cancer cells not only induces tumor growth but also directly contributes to cell proliferation. Thus, inhibitors targeting MK will be more effective than those that inhibit cancer cell proliferation alone. Our research is helpful for future work on MK and its applying to cure tumors.