The inhibitory effect of MEG3/miR 214/AIFM2 axis on the growth of T cell lymphoblastic lymphoma.
T cell lymphoblastic lymphoma (T LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non coding RNA (lncRNA) MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T LBL. Suppressed expression of MEG3 was detected in T LBL tissues compared with adjacent histologically normal tissues. Down regulated level of MEG3 was also found in three T LBL cell lines (CCRF CEM, Jurkat and SUP T1) compared with human T cell line H9. The proliferation of T LBL cells was inhibited and cell apoptosis rate was largely promoted when MEG3 was upregulated by a lentiviral vector. Further research revealed that microRNA (miRNA) 214 is a direct target of MEG3. The expression of miR 214 was increased in T LBL tissues and cell lines compared with control groups. Besides, decreased level of miR 214 was elevated adding miR 214 mimic in SUP T1 cells transfected with LncRNA MEG3. Similarly, upregulated level of miR 214 was downregulated adding miR 214 inhibitor in SUP T1 cells transfected with MEG3 siRNA. Luciferase activity assay further confirmed the targeting relationship between MEG3 and miR 214. Moreover, AIFM2 protein was predicted as a target of miR 214. The expression of AIFM2 was increased by MEG3 and was downregulated by miR 214 mimic. miRNA 214 reversed the effect of MEG3 on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest in SUP T1 cells. Moreover, relative expression of AIFM2 had a positive correlation with the expression of MEG3 and was negatively affected by miR 214. In vivo, MEG3 effectively suppressed tumor growth and the expression of proliferation markers Ki 67 and proliferating cell nuclear antigen (PCNA) Taken together, our research revealed that MEG3 worked as an anti oncogene in T LBL, and the MEG3 miR 214 AIFM2 pathway regulated the growth of T LBL, providing potential prognosis markers as well as new potential targets for T LBL treatment.
International journal of oncology