The long noncoding RNA Malati has been reported to be an oncogene that promotes tumor progress and correlates with prognosis in glioma. Growing evidence shows that autophagy plays a very important role in tumorigenesis and tumor cell survival, but whether Malatl regulates autophagy in glioma is still unclear. In this study, we found that Malatl expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malatl level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malatl significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malatl-induced cell proliferation. These data demonstrated that Malatl activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malatl functioned on glioma cell autophagy and proliferation. We found that Malati served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malati abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malatl-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malatl activates autophagy and promotes cell proliferation by sponging miR101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells. (C) 2017 Elsevier Inc. All rights reserved.