Derived from brain glial cells， gliomas are currently the most common primary tumours in the central nervous system and are characterised by a high recurrence rate and poor prognosis. RWDD3 (RWD domain-containing sumoylation enhancer， also termed RSUME)， which can be induced by cellular stress， such as CoCl2， heat shock and hypoxia， may play a crucial role in tumour angiogenesis， growth and metastasis. MicroRNAs (miRNAs) have been demonstrated to act as negative regulators of post-transcriptional gene expression and are involved in tumour growth and metastasis. In the present study， we explored the role of RWDD3 in glioma cell proliferation and invasion by the knockdown of RWDD3 with lentiviral shRNA and demonstrated that miRNA hsa-miR-375， regulates RWDD3 and has an important role in glioma progression. We found that expression of RWDD3 in high-grade gliomas was significantly higher than that noted in normal brain tissues and lower-grade gliomas in vivo. Knockdown of RWDD3 effectively led to cell cycle arrest， decreased proliferation and invasion， and increased apoptosis in human glioma cell lines. Furthermore， miR-375 was downregulated in human gliomas and overexpression of miR-375 caused downregulation of RWDD3 in glioma cells as well as inhibited their motility. Thus， these findings suggest that RWDD3 and miR-375 may function as therapeutic biomarkers for glioma patients.