MiR-122 inhibits cell proliferation and induces apoptosis by targeting runt-related transcription factors 2 in human glioma

摘要

OBJECTIVE: Accumulating evidence has suggested that microRNAs play critical roles in the development and progression of human glioma. The role of miR-122 in glioma tumorigenesis has been poorly defined. The current study is designed to investigate whether and how miR-122 affects proliferation and apoptosis of human glioma cells. PATIENTS AND METHODS: 8 normal brain tissues and 19 glioma tissues (7 for low grade and 12 for high grade) were collected. The expressions of miR-122 and runt-related transcription factors (RUNX2) in normal brain/glioma tissues and normal astrocytes (NHA)/multiple glioma cell lines (U87, U251, and U118) were analyzed by Real-time polymerase chain reaction (PCR). Western blot and luciferase activity assays were performed to validate the predicted relationship between miR-122 and RUNX2. The effects of miR-122 on cell proliferation and apoptosis were assessed by cell counting kit-8 (CCK-8), colony forming, and Annexin V-FITC/PI apoptosis assays using both gain- and loss-of-function approaches. RESULTS: MiR-122 expression is downregulated in glioma tissues compared with normal brain tissues, and is negatively correlated with the WHO grade. In contrast, the RUNX2 expression is upregulated in glioma tissues, and is positively correlated with the WHO grade. In glioma cell lines, the miR-122 expression is also constantly downregulated. MiR-122 functions as a tumor suppressor by inhibiting proliferation and inducing apoptosis, which is achieved by directly targeting RUNX2. Overexpression of RUNX2 can partially abrogate the effect of miR-122 on glioma cells. CONCLUSIONS: These results demonstrate a crucial role of miR-122 in regulating cell proliferation and apoptosis. Identifying the miR-122/RUNX2 signaling provides novel insights into the development of therapeutic targets for glioma.