Role And Mechanism Of Uc.133 On The Development Of B Cell Lymphoma

[Aims]Lymphoma is a common malignant tumor in China and its incidence is increasing in recent years,although some effects can be obtained by corresponding treatments,there are still a lot of refractory or recurrent cases with poor prognosis.Molecular targeted therapy is an important study for lymphoma.Ultra-conserved RNA is a kind of newly discovered long non-coding RNA in recent years,a lot of studies have found that ultraconserved RNA has close relationship with the development,metastasis,invasion and prognosis of tumors.In this study,we investigated the role and mechanism of uc.133 on the development of B cell lymphoma.We detected the level of uc.133 in the B cell lymphoma mice model and tissue from human B-cell lymphoma and normal human,and detected the RSRC1 levels in above tissues to reveal the mechanism.[Methods]1.The mice were injected with 4-hydroxytamoxifen(4-OHT)to activate the p53,mice were sacrificed and dissected the tumor tissue at 0min、10min、15min、30 min after 4-OHT injection.The qRT-PCR was performed to detect the levels of 4 UCRs screened by the microarray.Then We detected the 4 UCRs on B cell from bone marrow in the B cell lymphoma mice model and normal mice to screen the UCR with significantly expression difference.2.After the experiment of part 1,we have screened the uc.133 as the target UCR.We transfected the 293T cells with uc 133 plasmid and MSCV empty vector,then infected 38B9 cells and Romas cells respectively with virus.We got cells with infection rates of more than 90%after puromycin selection.3.We detected the proliferation and apoptosis of 38B9 cells and Romas cell over-expressing uc.133.Then we injected the cells over-expressing uc.133 subcutaneously to the BALB/c mice and detect the size of tumor.Two weeks after the cells injection,we dissected the size of tumor and the expression of RSRC1 by Western Blotting and immunohistology.[Results]1.qRT-PCR testing shows that level of uc.133、uc.268、uc.316A、uc.95 increased after 0min、10min、15min、30min after p53 activation.There are sifnificant expression differences in bone marrow of lymphoma mouse and that of normal mice.The greatest expression difference between model and normal mice is uc.133.2.We got uc.133 over-expression plasmids and MSCV empty vector virus and transfected them into 293T cells and packing to get the virus,then we used the virus infected 38B9 cells and Romas cells,we finally got the cells with infection rate of 96%after puromycin selection cells.3.The proliferation of 38B9 cells and Romas cells over-expression uc.133 showed lower while more apoptosis than control group.The size of tumors formed by 38B9 over-expressing uc.133 was significantly smaller than that of control,Romas cells over-expressing uc.133 did not form any tumor.We found that RSRC1 level of 38B9 cells and Romas cells over-expressing uc.133 is higher than that of control cells.[Conclusions]uc.133 played an important antitumor effect during the occurance and development of B-cell lymphoma.