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MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
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MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
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Journal Article
MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44
2021
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Brain Neoplasms - metabolism
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Hyaluronan Receptors - genetics
/ Hyaluronan Receptors - metabolism
/ Kinases
/ Mice
/ miRNA
/ Science
/ Survival
/ Tumors
