Abstract LB175: MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44 and sensitizes to temozolomide

Abstract

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 pinpoint tumor suppressive miRNAs with therapeutic potential against GBM, one of the most deadly cancers. Whole transcriptome and miRNA expression profiling analyses were performed on human GBM patient tissues. Transient transfection of miRNA mimics was used to investigate the tumor suppressive role of a miRNA (miR-138) in cell proliferation, cell cycle, migration, would healing, and chemosensitivity to temozolomide (TMZ). Orthotopic xenograft mice model using human patient-derived primary GBM cells was used for the survival studies. miR-138 was found as one of the most significantly downregulated miRNAs with an inverse correlation with CD44 expression. Functional studies unveiled that miR-138 negatively regulates the expression of CD44 at protein level by directly binding to the 3’ UTR of CD44. CD44 inhibition by miR-138 overexpression 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 addition, miR-138 sensitized GBM tumor to TMZ in mice. We demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 and sensitization to chemotherapy for the treatment of primary and even chemoresistant GBM Citation Format: Tae Jin Lee, Ji Young Yoo, Deokhwa Nam, Ji Seon Shim, Alberto Bueso-Perez, Balveen Kaur. MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44 and sensitizes to temozolomide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB175.