MicroRNA-153 is tumor suppressive in glioblastoma stem cells

Abstract

Glioblastoma multiforme (GBM) is lethal brain tumor thought to arise from GBM stem cells (GBM-SCs). MicroRNAs carry out post-transcriptional regulation of various cellular processes that modulate the stemness properties of GBM-SCs. Here, we investigated the critical role of miR-153 in GBM-SCs. First, GBM-SCs were isolated from six GBM specimens. These GBM-SCs formed GBM spheres, expressed markers associated with neural stem cells, and possessed the capacity for self-renewal and multilineage differentiation. Then qRT-PCR analysis showed that miR-153 expression was down-regulated in GBM tissues relative to normal brain tissues, and in CD133 positive cells relative to CD133 negative cells. This project demonstrates for the first time that transient transfection of miR-153 into GBM-SCs can inhibit their stemness properties, such as impairing self-renewal ability and inducing differentiation. Meanwhile, miR-153 can also repress GBM-SCs growth and induce apoptosis. Altogether, these results indicate that reactivation of miR-153 expression suggests novel therapeutic strategies for GBM-SCs.

miR-153 Silencing Induces Apoptosis in the MDA-MB-231 Breast Cancer Cell Line

“…Furthermore, antiapoptotic protein Bcl-2 and induced myeloid leukemia cell differentiation protein (Mcl-1) were downregulated by miR-153 upregulation. Zhao et al (2013) discovered that transient transfection of miR-153 in glioblastoma stem cells induces apoptosis. Furthermore, low expression level of miR-153 was found to be significantly related to metastasis and poor prognosis in oral cancer patients by targeting SNAI1 and ZEB2 (Xu et al, 2013).…”

MicroRNA Regulating Glutathione S-Transferase P1 in Prostate Cancer

“…Studies conducted using various human prostate cancer cell lines demonstrate miR-153 represses PTEN expression to activate AKT kinase and downregulate the transcriptional activity of Forkhead box O (FOXO)1, leading to upregulation of the G1/S transitional promoter cyclin D1 and downregulation of the cyclin-dependent kinase (CDK) inhibitor p21 [98]. In contrast, miR-153 levels are shown to be reduced in human glioblastoma multiforme [99]. miR-153 induces apoptosis in these tumors by targeting Bcl-2 and Mcl-1, suggesting that miR-153 functions as a tumor suppressor [100].…”

“…miR-153 induces apoptosis in these tumors by targeting Bcl-2 and Mcl-1, suggesting that miR-153 functions as a tumor suppressor [100]. Studies have revealed a tendency toward downregulation of miR-153 in relation to lymph node metastasis in ovarian epithelial tumors [101], and downregulation of miR-153 in high-risk medulloblastomas [99]. Therefore, miR-153 may function as a tumor suppressor or an oncogene depending on the tissue.…”

MicroRNA-profiling in breast- and salivary gland-derived adenoid cystic carcinomas

“…A miRNS-ek szerepe napjainkban talán leginkább a daganatpatológiában kap a legtöbb figyelmet, hiszen ezek a kis molekulák a gének poszttranszkripcionális szabályozása révén hozzájárulnak a daganatos szövet kialakulásához, növekedéséhez és tovaterjedéséhez is, így egyes esetekben akár biomarkerként is felhasználhatóak lehetnek [25,26]. Klinikai alkalmazásuk reményében a miRNS-ek szintjét manapság már szinte kivétel nélkül minden daganattípus-ban kiterjedten vizsgálják: tüdődaganatokban [27,28], emlőtumorokban [29,30], a vastagbél, a prosztata és a máj rosszindulatú [31,32,33] elváltozásaiban, de ritkábban előforduló tumorok esetében is, így agyda-ganatokban [34] vagy a mellékvesekéregből kiinduló rosszindulatú folyamatokban is [35].…”