miR-665 is downregulated in glioma and inhibits tumor cell proliferation, migration and invasion by targeting high mobility group box 1

摘要

Glioma is the most common brain tumor in adults. microRNAs (miRNAs/miRs) play an essential role in tumor development and progression. The present study aimed to investigate the potential clinical significance and function of miR-665 in glioma. Reverse transcription-quantitative PCR analysis was used to detect the expression of miR-665 in glioma tissues and cells. Survival curves were constructed using the Kaplan-Meier method. Cox regression analysis was performed to investigate the prognostic significance of miR-665. Cell Counting Kit-8 and Transwell assays were used to evaluate the role of miR-665 in glioma. Bioinformatics analysis and Dual-luciferase reporter assays were used to predict the putative direct targets of miR-665. Western blotting was used to evaluate the activity of the Wnt/beta-catenin pathway. The relative expression of miR-665 was decreased in glioma tissues and cells and this downregulation was significantly associated with the Karnofsky performance scale score and World Health Organisation grade. Patients with glioma with low miR-665 expression had a shorter overall survival time compared with the high expression group. Besides, overexpression of miR-665 suppressed the proliferation, migration and invasion of glioma cells, while knockdown of miR-665 promoted these cellular behaviors. High mobility group box (HMGB)1 was a direct target of miR-665. It was also demonstrated that miR-665 may suppress glioma progression by targeting HMGB1 and inhibiting the Wnt/beta-catenin pathway. Taken together, these data suggested that miR-665 may have a tumor suppressor role in glioma by targeting HMGB1. Therefore, miR-665 may be a novel prognostic biomarker and the miR-665/HMGB1 axis may be a novel therapeutic target for the treatment of glioma.