MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44.

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.

• 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
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 9219 (04 28 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 33911148 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CD44 protein, human
• Hyaluronan Receptors
• MIRN138 microRNA, human
• MicroRNAs

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Glioblastoma (genetics, metabolism, pathology)
• Humans
• Hyaluronan Receptors (genetics, metabolism)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• MicroRNAs (genetics)
• Prognosis
• Survival Rate
• Transcriptome
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays