MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44

• Main Authors: Margaret Yeh, Yin-Ying Wang, Ji Young Yoo, Christina Oh, Yoshihiro Otani, Jin Muk Kang, Eun S. Park, Eunhee Kim, Sangwoon Chung, Young-Jun Jeon, George A. Calin, Balveen Kaur, Zhongming Zhao, Tae Jin Lee
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-04-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-021-88615-8

Abstract Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one of the significantly downregulated miRNAs with an inverse correlation with CD44 expression. Transient overexpression of miR-138 in GBM cells inhibited cell proliferation, cell cycle, migration, and wound healing capability. We unveiled that miR-138 negatively regulates the expression of CD44 by directly binding to the 3′ UTR of CD44. CD44 inhibition by miR-138 resulted in an inhibition of glioblastoma cell proliferation in vitro through cell cycle arrest as evidenced by a significant induction of p27 and its translocation into nucleus. Ectopic expression of miR-138 also increased survival rates in mice that had an intracranial xenograft tumor derived from human patient-derived primary GBM cells. In conclusion, we demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 for the treatment of primary GBM.