MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44

• Published in: Scientific reports Vol. 11; no. 1; pp. 9219 - 11
• Main Authors: Yeh, Margaret, Wang, Yin-Ying, Yoo, Ji Young, Oh, Christina, Otani, Yoshihiro, Kang, Jin Muk, Park, Eun S., Kim, Eunhee, Chung, Sangwoon, Jeon, Young-Jun, Calin, George A., Kaur, Balveen, Zhao, Zhongming, Lee, Tae Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 3' Untranslated regions; 631/337/384/331; 631/67/1922; Animals; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; CD44 antigen; Cell Cycle; Cell growth; Cell migration; Cell Movement; Cell Proliferation; Ectopic expression; Gene expression; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Humanities and Social Sciences; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Kinases; Mice; Mice, Inbred NOD; Mice, SCID; MicroRNAs; MicroRNAs - genetics; miRNA; multidisciplinary; Prognosis; Science; Science (multidisciplinary); Survival; Survival Rate; Transcriptome; Transcriptomes; Translocation; Tumor Cells, Cultured; Tumors; Wound healing; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-88615-8

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.