LncRNA-MALAT1 Suppresses Glioma Cell Proliferation And Invasion By Targeting The ERK/MAPK Signaling Pathway

ObjectiveGlioma is one of the most common types of primary brain tumors in adults, and represents one of the most aggressive and lethal human cancer types. Although individualized treatment such as radiotherapy and chemotherapy was given according to the standard after surgery, but the prognosis remains poor because of rapid proliferation, its aggressive potential, and its resistance to chemotherapy or radiotherapy. The average survival of glioblastoma is 15 to18 months. More and more evidences prove that abnormal expression of MALAT1 was related to the occurrence、development recurrence and prognosis of malignant tumor. Long noncoding RNAs(lncRNAs) are types of transcriptional products of the eukaryotic genome comprising >200 nt in length. Its abnormal expression can regulate the expression of some certain genes in epigenetics, transcription, and after the transcription level. It is reported that MALAT1 has a significant difference in many kinds of tumors, and it could play a role of oncogene through certain signaling pathways. However, the study of MALAT1 in glioma is limited. Thus, this study study was conducted to explore the expression in glioma by qPCR. Subsequently, molecular funcyions of lncRNA-MALAT1 in glioma cell lines were studied.MethodsFor the study, 132 glioma samples and 20 non-neoplastic brain tissue samples were obtained between 2010 and 2013 from the Department of Neurosurgery, Brain and Nerve Research Laboratory of The First Affiliated Hospital of Soochow University. The expression of MALAT1 was detected in tissue samples using qRT-PCR. Lentivirus vectors encoding lncRNA-MALAT1 and anti-MALAT1 were constructed and stably transfected into U87 and U251 cells. Then the proliferation and invasion ability of the cells were tested. The expression of protein related to ERK/MAPK signaling pathway was analyzed by western blot.ResultsIn this study, quantitative reverse transcription polymerase chain reaction(qRT-PCR) was used to demonstrate that the expression of MALAT1 was lower than that in normal brain tissues. Stable RNA interference-mediated knockdown of MALAT1 in human glioma cell lines(U87 and U251) significantly promoted the invasion and proliferation of the glioma cells by in vitro assays. Conversely, overexpression of MALAT1 caused significant reduction in cell proliferation and invasion in vitro, and tumorigenicity in both subcutaneous and intracranial human glioma xenograft models. Furthermore, MALAT1-mediated tumor suppression in glioma cells may be via reduction of extracellular signal-regulated kinase/mitogen-activated protein kinase(ERK/MAPK) signaling activity and expression of matrix metalloproteinase 2(MMP2).ConclusionIn conclusion, overall data demonstrated the tumor-suppressive role of MALAT1 in glioma by attenuating ERK/MAPK-mediated growth and MMP2-mediated invasiveness.