title: Targeting glioma stem cells by functional inhibition of a prosurvival oncomiR-138 in malignant gliomas.
abstract: Malignant gliomas are the most aggressive forms of brain tumors, associated with high rates of morbidity and mortality. Recurrence and tumorigenesis are attributed to a subpopulation of tumor-initiating glioma stem cells (GSCs) that are intrinsically resistant to therapy. Initiation and progression of gliomas have been linked to alterations in microRNA expression. Here, we report the identification of microRNA-138 (miR-138) as a molecular signature of GSCs and demonstrate a vital role for miR-138 in promoting growth and survival of bona fide tumor-initiating cells with self-renewal potential. Sequence-specific functional inhibition of miR-138 prevents tumorsphere formation in vitro and impedes tumorigenesis in vivo. We delineate the components of the miR-138 regulatory network by loss-of-function analysis to identify specific regulators of apoptosis. Finally, the higher expression of miR-138 in GSCs compared to non-neoplastic tissue and association with tumor recurrence and survival highlights the clinical significance of miR-138 as a prognostic biomarker and a therapeutic target for treatment of malignant gliomas.
authors.affiliation: Institute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, Singapore.
authors.forename: Xin Hui Derryn
authors.initials: XH
authors.lastname: Chan
authors.forename: Srikanth
authors.initials: S
authors.lastname: Nama
authors.forename: Felicia
authors.initials: F
authors.lastname: Gopal
authors.forename: Pamela
authors.initials: P
authors.lastname: Rizk
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Gopinath
authors.initials: G
authors.lastname: Sundaram
authors.forename: Ghim Siong
authors.initials: GS
authors.lastname: Ow
authors.forename: Anna Vladimirovna
authors.initials: AV
authors.lastname: Ivshina
authors.forename: Vivek
authors.initials: V
authors.lastname: Tanavde
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kuznetsov
authors.forename: Prabha
authors.initials: P
authors.lastname: Sampath
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm